Myeloma Today Summer 2021

Volume 21 Number 3

Summer 2021

Myeloma Today A publication of the International Myeloma Foundation

12th ANNUAL

IMWG Summit 2021

ighlights of myeloma }H

presentations at the 2021 ASCO & EHA Annual Meetings PAGE 4

eport from the 2021 }R

Summit of the International Myeloma Working Group PAGE 5

enetoclax clinical trials }V

show efficacy in t(11;14) multiple myeloma PAGE 8

This edition of Myeloma Today is supported by AbbVie • Amgen • Bristol Myers Squibb • Karyopharm Therapeutics • Sanofi Genzyme • Takeda Oncology

International Myeloma Foundation

Founder

President & CEO

Brian D. Novis

Susie Durie

Board of Directors

Chairman Dr. Brian G.M. Durie Christine Battistini Yelak Biru Prof. Dr. Mario Boccadoro Loraine Boyle Susie Durie

Martine Elias George T. Hayum Jason Katz Benson Klein Andrew Kuzneski, III

Dr. Robert A. Kyle Prof. Dr. Heinz Ludwig Dr. Edith Mitchell Charles Newman Dr. S. Vincent Rajkumar

Matthew Robinson E. Michael D. Scott

IMF Executive Team Chief Financial Officer Jennifer Scarne jscarne@myeloma.org

Senior Vice President, Strategic Planning Diane Moran dmoran@myeloma.org

Senior Vice President, Clinical Education & Research Initiatives Lisa Paik lpaik@myeloma.org

Senior Vice President, Global Affairs Daniel Navid dnavid@myeloma.org

Chief Medical Officer Dr. Joseph Mikhael jmikhael@myeloma.org

Senior Vice President, Philanthropy Lynn K. Green, Ed.D. lgreen@myeloma.org

Senior Vice President, Global Advocacy, Access, Policy & Research Mimi Choon-Quinones, PhD, MBA mchoon-quinones@myeloma.org

Vice President, Marketing Peter Anton panton@myeloma.org

Inventory Control Manager Betty Arevalo marevalo@myeloma.org

Meeting Registration & Guest Relations Abigail Guzman aguzman@myeloma.org

Assistant to Senior Director, Member Events Karla Lemus klemus@myeloma.org

Web Producer Miko Santos msantos@myeloma.org

Director, Regional Community Workshops Brenda Hawkes bhawkes@myeloma.org

Senior Director, Public Policy & Advocacy Robin Levy rlevy@myeloma.org

Regional Director, Support Groups Kelley Sidorowicz ksidorowicz@myeloma.org

Senior Research Project Coordinator Amirah Limayo alimayo@myeloma.org

Donor Relations Sarah Solomon ssolomon@myeloma.org

Coordinator, Marketing & Communications Jason London jlondon@myeloma.org

Accounting & Distribution Brando Sordoni bsordoni@myeloma.org

IMF Staff

Senior Director, Member Events Suzanne Battaglia sbattaglia@myeloma.org Regional Director, Support Groups Nancy Bruno nbruno@myeloma.org Director, Support Groups & Regional Community Workshops Kelly Cox kcox@myeloma.org Director, Public Policy & Advocacy Danielle Doheny ddoheny@myeloma.org Director, Global Myeloma Action Network and European & Middle Eastern Patient Programs Serdar Erdoğan serdogan@myeloma.org Donor Relations Heather Fishman hfishman@myeloma.org Support Group Coordinator Jon Fitzpatrick jfitzpatrick@myeloma.org

InfoLine Coordinator Paul Hewitt phewitt@myeloma.org Web Specialist Kevin Huynh khuynh@myeloma.org Editor-in-Chief, Publications Marya Kazakova mkazakova@myeloma.org

Publication Design Jim Needham jneedham@myeloma.org

Assistant Director, Member Events Ilana Kenville ikenville@myeloma.org

Administrative Assistant, Meetings & Events Meghan O’Connor moconnor@myeloma.org

InfoLine Coordinator Missy Klepetar mklepetar@myeloma.org

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Accountant Phil Lange plange@myeloma.org

Database Analyst Joy Riznikove jriznikove@myeloma.org

Assistant to the President Rafi Stephan rstephan@myeloma.org Vice President, Support Groups Robin Tuohy rtuohy@myeloma.org InfoLine Coordinator Judy Webb jwebb@myeloma.org Donor Relations Jonathan Weitz jweitz@myeloma.org

This free issue of Myeloma Today© (Volume 21, Number 3) is dated July 30, 2021. Myeloma Today© is a quarterly (Spring, Summer, Fall, and Winter) publication of the International Myeloma Foundation, located at 12650 Riverside Drive, Suite 206, North Hollywood, CA 91607 USA

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A Message from the IMF President and the IMF Chairman Dear Reader, In May 2021, the prestigious Blood Cancer Journal published the first results of the iStopMM (Iceland Screens, Treats, or Prevents Multiple Myeloma) study, the very first country-wide project of its kind ever attempted, much less successfully conducted. The accrual alone was an amazing achievement – more than 80,000 volunteer participants! It is so gratifying to know that people whose lives haven’t been touched by myeloma are happy to contribute to the ongoing learning about this disease. They want to help and be involved in our research.

There is now a dedicated clinic for the testing and follow-up of all iStopMM participants with the key goal of assessing the value of early screening. The potential benefits of early screening are well established in myeloma. Starting treatment at an earlier stage of disease leads to better outcomes, with longer remission and improved overall survival. The iStopMM project was specifically structured to capture any potential downsides to screening, such as negative psychological impact of becoming aware of an early abnormality that requires monitoring but not treatment. The initial findings by principal investigator Dr. Sigurdur Kristinsson of the University of Iceland are very encouraging.

Study participants do not develop increased anxiety or other negative effects. Regular monitoring will continue to assess the longer-term impacts, but so far so good!

Screening such a huge number of individuals is an enormous feat. A highly sensitive method called “mass spectrometry” is used to test for proteins in the blood, and it is already revealing some information. But there is much more to be learned about the earliest stages of myeloma. The costs of mass spectrometry testing are low when compared to general medical testing or the much higher costs of treatment for active myeloma.

The iStopMM project has the capacity for testing to be used in a correlated fashion. A major advantage of the study being located in Iceland is the testing conducted by deCODE Genetics for the whole Icelandic population. The iStopMM participants who develop MGUS, smoldering myeloma, or active myeloma can be compared at the genetic level with the more than 300,000 others in the Icelandic population who do not develop disease. Comprehensive tissue banking is an additional part of

iStopMM, and it will enable many innovative research studies in the future.

The follow-up study will yield groundbreaking data about the biology of early myeloma and the value of early diagnosis, and will also shed light on the possibility of truly preventing the development of myeloma, as well as the optimal interventions to achieve a cure for those who are diagnosed. These are the fundamental goals of the IMF’s Black Swan Research Initiative® (BSRI®) and for all of us in the myeloma community.

The ambitious iStopMM study was launched in November 2016 as part of BSRI. Iceland’s size, the service-oriented mindset of its citizens, the endorsements of national leaders, and an effective social media campaign amplified the call for volunteers.

Over 54% of Icelandic residents born before 1976 have signed up for the study, the highest clinical trial participation ever for a single country. To watch the video announcement, go to youtu.be/LskOC39mYx8.

It is truly wonderful to see this project moving so strongly forward! Expectations are high and we will keep you posted each step of the way!

Warm regards,

Susie Durie, IMF President & CEO

Dr. Brian G.M. Durie, IMF Chairman

Dr. Sigurdur Kristinsson (on the far right) with his iStopMM Dream Team!

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Scientific & Clinical

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JO R D S EI

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2021 ASCO and EHA Meeting Overview

By Dr. Joseph Mikhael IMF Chief Medical Officer

The annual meeting of the American Society of Clinical Oncology (ASCO) was held June 4-8, 2021. There were many myelomarelated oral and poster presentations, and I would like to share with you several themes that emerged from this year’s meeting.

Induction therapy Induction is the initial treatment given to patients who are newly diagnosed with myeloma. More and more clinical trials that compare 4-drug (quadruplet) combination therapy to 3-drug (triplet) therapy are demonstrating the benefit of quadruplets, which can achieve a very deep response. In general, this means adding Darzalex (daratumumab) or Sarclisa (isatuximab) to a combination such as VRd (Velcade [bortezomib] + Revlimid [lenalidomide] + dexamethasone) or KRd (Kyprolis [carfilzomib] + Rd). This is especially true for patients who intend to proceed to an autologous stem cell transplant (ASCT).

Transplantation ASCT remains the standard of care in myeloma, and we continue to gain data that show the benefit of ASCT. The FORTE study demonstrated that KRd induction therapy followed by consolidation therapy with ASCT was superior to receiving KRd alone.

Maintenance therapy The FORTE study also then randomized patients after initial treatment to either receive R (Revlimid) maintenance or KR (Kyprolis + Revlimid) maintenance. Patients who had KR clearly benefited in that they remained in remission for significantly longer; the 3-year progression free survival (PFS) rate was 90% in standard-risk patients. Furthermore, KR also seemed to benefit high-risk patients.

The follow-up of the CASSIOPEIA study, which compared DaraVTd (Darzalex + Velcade + thalidomide + dexamethasone) vs.

VTd, showed that Darzalex was better than placebo for maintenance therapy. However, in patients who received Darzalex with VTd for induction/consolidation, the addition of Darzalex maintenance showed no added benefit and did not prolong remissions. More study data is needed to evaluate how long we need a quadruplet during induction.

High-risk myeloma Many clinical trials are including careful evaluation of patients who have high-risk myeloma with chromosomal abnormalities.

More intense approaches are being explored as high-risk disease has inferior outcomes.

More options in relapsed myeloma Matching the trend of introducing new mechanisms of action through novel therapies in relapsed myeloma, more data was presented on the use of Xpovio (selinexor) in combination with other agents. In the STOMP study, the all-oral combination of XPd (Xpovio + Pomalyst [pomalidomide] + dexamethasone) at a lower dose of 60 mg is better tolerated weekly. (The FDA has approved Xpovio at 100 mg once per week.) XPd is an important regimen for triple-class exposed patients. While the dosing is still being optimized in the XKd combination with Kyprolis, this regimen is an important combination in relapse as it provides an option when Velcade is not preferred. XPd and XKd both show efficacy in patients previously treated with Darzalex or Sarclisa.

Weekly Xpovio makes managing nausea easier, especially when two anti-emetic drugs are used. Furthermore, the FDA-approved XVd regimen from the BOSTON study had further analyses showing that it remains effective in patients who relapse on Revlimid, in patients over the age of 65, and in patients with high-risk disease.

Emerging therapies The CAR T-cell therapy “cilta-cel” has demonstrated an unprecedented 98% overall response rate (ORR) in relapsed and refractory myeloma. At 18 months, 66% of patients remained in remission, with an overall survival (OS) of 81%. These kinds of response rates can change the landscape of myeloma for the future. Several other CAR T-cell treatment approaches are being explored.

We also saw data from studies of bispecific antibody therapies. Updated results on 40 heavily pretreated patients in a phase II study with teclistamab demonstrated that 58% of responders had a very good partial response (VGPR) and 30% had a complete response (CR) or better. Several other bispecific therapies are being explored, some with BCMA as the target and also using new targets such as GPRC5D and FCRH5.

Iberdomide, a novel cereblon E3 ligase modulator (CelMod), is being tested in combination with proteasome inhibitors and also with CD38-targeting monoclonal antibodies, in order to evaluate optimal dose and safety in patients with relapsed/refractory myeloma.

EHA meeting The annual meeting of the European Hematology Association (EHA) was held virtually June 9-17, 2021. A late-breaking oral session on June 12 shed light on long-term management of (continues on page 14)

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Scientific & Clinical

Highlights of the 2021 Summit of the International Myeloma Working Group

By Dr. Brian G.M. Durie IMF Chairman of the Board

12th ANNUAL

The 12th Annual Summit of the IMF’s International Myeloma Working Group (IMWG) took place June 22nd and 23rd, 2021.

The IMWG is the most prestigious organization for myeloma researchers from around the world. Creating, supporting, and hosting the important work of the IMWG and its members is a critical element of the IMF’s mission to expand myeloma research and to educate myeloma patients on a global level.

The IMWG Summit is a key annual activity for many of the world’s top myeloma experts who collaborate on imperative projects throughout the year. The mission of the Summit is to identify, support, and implement the most promising research to prevent the onset of active disease, to improve treatment, and to find a cure. In 2021, for the second year in a row, the IMWG Summit was held in virtual format.

More than 100 IMWG members were invited to join an online platform that supported optimal participation in discussions of the greatest current importance in myeloma. The Chairpersons of the IMWG Summit are Drs. Brian G.M. Durie and S. Vincent Rajkumar. The Co-leaders are Drs. Jesús San-Miguel, Philippe Moreau, and Nikhil Munshi. The meeting agenda spanned two days, with the plenary session on day one, and the IMWG awards ceremony on day two, followed by reports from the working group committees. The Summit opened with welcome remarks from the IMF President Susie Durie and Summit Chairpersons, Drs. Durie and Rajkumar.

HR SMM Dr. Shaji Kumar led the first session, a discussion of the 2/20/20 risk stratification model for high-risk smoldering multiple myeloma (HR SMM). This important advancement was developed as a result of an IMWG research project and published in Blood Cancer Journal in October 2020. Data was gathered from a large number of international sites to assess patients with SMM who progressed, or those who did not. The 2/20/20 system was devised in a collaboration between Dr. Kumar and Dr. Durie with the Spanish team led by Dr. Jesús San-Miguel and María-Victoria Mateos. A cohort of 1,996 patients with SMM was analyzed and three factors predicting progression risk at 2 years were identified: serum M-protein >2 g/dL, involved to uninvolved free light-chain ratio >20, and marrow plasma cell infiltration >20%.

The 2/20/20 risk stratification model is widely applicable and is predictive of progression from HR SMM to active myeloma.

The IMWG also developed a point-scoring system and an online calculator app to identify ultra-high-risk SMM, a group for which immediate treatment can be strongly considered. Patients who score 12 or more points have ultra-high-risk SMM and are eligible for treatment. In the context of planning a randomized 800.452.CURE toll-free in USA and Canada

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IMWG Summit 2021

phase III clinical trial, Revlimid® (lenalidomide) is recommended as the control arm. Phase II studies will assess if more aggressive approaches can achieve a cure for some patients.

Dr. Mateos presented the current data on HR SMM treatment.

The QuiRedex multicenter, open-label, randomized phase III clinical trial of Revlimid + dexamethasone (Rd) vs. no treatment showed that early treatment does not induce more resistant relapses. The E3A06 study of Revlimid vs. observation in patients with asymptomatic SMM showed that treatment with Revlimid significantly prevented the progression to active disease, especially in HR SMM. These two trials support early treatment of HR SMM, and numerous clinical trials are currently ongoing.

The IMWG is continuing to evaluate curative strategies in the CESAR and the ASCENT clinical trials, with the ASCENT study nearing completion.

The efficacy of therapies containing Revlimid + dexamethasone with other agents seems to be superior in intermediate-high-risk SMM patients than in MM. Studies are ongoing.

Quadruplets vs. triplets Dr. Moreau led the discussion of 4-drug (quadruplet) vs. 3-drug (triplet) therapies. As demonstrated by the CASSIOPEIA study of D-VTd vs. VTd, as well as the GRIFFIN study with D-VRd vs. VRd, the excellent outcome with the quadruplets makes it clear that quadruplets are outperforming triplets.

Dr. Rajkumar presented on early vs. delayed autologous stem cell transplant (ASCT). Although remissions are longer with early ASCT as demonstrated in the French IFM study of VRd with/without transplant, the overall survival continues to be equal to patients who delay ASCT. Patients who have a later transplant or other therapies can catch up. Therefore, particularly in view of the earlier use of CAR T-cell therapy or other immunotherapies as a consolidation approach, this may be the time to closely re-evaluate the role of ASCT in myeloma.

The strange paradox is that it will take likely longer than 20 years to confirm the value of triplet or quadruplet combinations or more aggressive approaches in achieving long-term, disease-free remission or cure. (continues on next page)

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Scientific & Clinical HIGHLIGHTS – IMWG SUMMIT 2021 – CONTINUED FROM PREVIOUS PAGE

Minimal residual disease Dr. Bruno Paiva addressed the standardization of MRD testing in clinical trials. Sustained MRD negativity during remission provides an excellent indicator of long-term benefit and there is little doubt of the high prognostic importance for MRD. There is an ongoing conversation about the ideal protocol to assess and demonstrate that MRD-negativity is a true surrogate as an indicator of treatment benefit that can be used instead of progression-free survival (PFS). Through the IMF’s Black Swan Research Initiative® we’re currently investigating even higher MRD sensitivity, such as 10–8 (zero myeloma cells out of 100 million cells).

Immunotherapies Drs. Nikhil Munshi, Tom Martin, and Yi Lin led discussions about current and next-generation CAR T-cell and other cellular therapies. CAR T-cell therapy confers a high percentage of deep responses with the CARTITUDE protocol – up to more than 90%! – with sustained responses for those having the deepest responses. There are still concerns about the early cytokine release syndrome (CRS) and, in some patients in the trial, neurotoxicity. The other important question is how will CAR T-cell therapy be made available to patients in the community setting? It’s not clear how patients will have access to specialized centers at this time.

A detailed discussion about the role of bispecific antibodies took a close look at exciting data that shows several bispecifics to be very active. There are concerns about toxicities, and some bispecific products have been withdrawn from clinical trials due to neurotoxicities. However, several studies, particularly with teclistamab, a bispecific antibody targeting both BCMA and CD3, are moving forward with excellent responses.

The big difference is that unlike the “one and done” CAR T-cell therapy, therapy with bispecifics is ongoing and high-intensity,

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which can be tough on patients. There are discussions about limiting the length of treatment with bispecifics to, for example, six months or so. There are also discussions about newer and next-generation products that are non-BCMA targeted.

Immune therapies registry Drs. Tom Martin and Yi Lin presented a report on the IMWG Immune Therapy Committee, sharing exciting news on major projects. The Committee has established a framework for a new IMWG Immune Therapies Registry to be housed at UCSF, which will collect data on patients receiving the new immune therapies that are used sequentially, including those with BCMA as a target (e.g., Blenrep®), the anti-BCMA CAR T-cell therapies (e.g., Abecma® and cilta-cel), and the bispecific antibodies currently in clinical trials. We already know that bispecifics can be effective after other BCMA-targeted therapies. The Immune Therapies Registry will become increasingly important in the coming years as more agents receive FDA approval.

Virtual tissue bank A Virtual Tissue Bank is in development as part of the Asian Myeloma Network (AMN), an IMF research division and clinical trials group. Dr. Wee Joo Chng has set up a system to standardize tissue collection, in which all participating centers can retain tissue samples at their sites. The sharing of information and analyses will enhance collaborative efforts, and it is extremely important to be able to measure the efficacies and toxicities that occur when immune therapies are used.

Mass Spectrometry Drs. David Murray and Brian Durie represented the Mass Spectrometry Committee. The hope is that using mass spectrometry or other innovative testing can become a reliable indicator of potential early relapse. Using mass spectrometry,

Brian G.M. Durie

S. Vincent Rajkumar

Philippe Moreau

Nikhil Munshi

Jesús San Miguel

María-Victoria Mateos

Thomas Martin

Bruno Paiva

Sagar Lonial

Shaji K. Kumar

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tiny monoclonal proteins are detectable at a very early time point. As many as 30% of such tiny “spikes” can disappear over time, having been triggered by infection or some other immune reaction. The discussion included how to best implement mass spec and make it routinely available, how to interpret the results and detect early relapse.

COVID-19 vaccination and MM Dr. Evangelos Terpos delivered the Summit Keynote Lecture on the role of COVID-19 vaccination for myeloma patients.

Unfortunately, vaccination does not produce the levels of neutralizing antibodies that we’d like to see. There was much disappointment in learning that some of the newer immune therapies, such as anti-CD38 and anti-BCMA products, impaired neutralizing antibody responses required for immunity against COVID-19. Discussion evolved to consider third “booster” shots for at-risk patients who are on such therapies and/or with low blood-lymphocyte levels, which is another risk factor. A study to assess booster shots will begin shortly in Greece. Another potential study will include early intervention with the use of monoclonal antibodies against COVID-19, such as a Regeneron product available in the US, or even a preventive approach for those at highest risk of COVID complications.

IMWG researchers also expressed great interest in addressing disparities in clinical trial access and accruals. There was an acknowledgement that major social disparities exist, making this an especially difficult problem to solve, but there is a major impetus to improve access for all disadvantaged groups.

Future discussions IMWG researchers and our industry partners suggested that to help address key clinical trial issues, we consider inviting representatives of the FDA and the European Medicines Agency (EMA) to future meetings, an idea that was met with enthusiasm.

We will also incorporate more real-world data analyses, including quality of life assessments. From these, better priorities can be established for drug selection and creation of optimal doses and schedules for emerging agents and combinations.

By any measure, the 2021 IMWG Summit was a wonderfully successful and productive event with lively interactions among participants who took full advantage of the opportunities to make plans for future research collaborations. But it was very clear that everyone is keen to get back to an in-person program in 2022! MT

Access to clinical trials Dr. Morie Gertz raised the question of how to manage relapsing patients in the real-world setting. A majority of patients with advanced disease are not eligible for clinical trials because their health status needs to be good, which is not often the case, in order to assess potential toxicities of drugs or drug combinations. Early, careful testing of new agents is required for safety reasons, but next-level studies can perhaps explore more challenging situations, such as those patients with very low bloodcount levels or compromised kidney or liver function.

Please visit videos.myeloma.org to view IMWG Conference Series: Making Sense of Treatment as well as the helpful Ask Dr. Durie videos. To read the Week in Review by Dr. Brian G.M. Durie blog series please visit blogs.myeloma.org.

Paul G. Richardson

Evangelos Terpos

Morie A. Gertz

Kenneth C. Anderson

Sigurður Y. Kristinsson

Yi Lin

Irene M. Ghobrial

David Murray

Pieter Sonneveld

Saad Usmani

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Scientific & Clinical

Venetoclax Trials Show Efficacy in t(11;14) MM Dr. Shaji K. Kumar Mayo Clinic, Rochester, Minnesota

Venetoclax is a B-cell lymphoma 2 (BCL-2) inhibitor approved by the US Food and Drug Administration (FDA) to treat lymphoma and leukemia. It is now being inves­tigated in myeloma for patients with specific genetic disease characteristics.

BCL-2 is a protein present in high amounts in cancer cells, helping the cancer cells survive and become resistant to treatment.

Venetoclax attaches to BCL-2 and blocks its actions, causing the death of cancer cells. Myeloma cells are dependent on BCL-2 for survival, and this dependency is affected in part by the presence of genetic abnormalities, such as t(11;14) translocation that is present in 15–20% of myeloma patients. Clinical trials have shown efficacy of venetoclax in myeloma, particularly in patients who test positive for the t(11;14) translocation biomarker.

Clinical trials in myeloma On clinicaltrials.gov you will find up-to-date information about the following three clinical trials.

NCT03539744: The CANOVA clinical trial is a phase III, mul-

ticenter, randomized, open label, international study that will compare venetoclax in combination with the steroid dexamethasone (VenDex) vs. the combination of Pomalyst® (pomalidomide) and dexamethasone (Pd) in 244 patients with t(11;14)-positive relapsed or refractory myeloma, and who have received at least two prior lines of therapy, including Revlimid® (lenalidomide) and a proteasome inhibitor. The overall objective of this study is to evaluate the safety and effectiveness of VenDex when compared with Pd. Once fully enrolled, there will be approximately 122 adult patients in each study arm. Patients in both study arms will receive treatments with oral (by mouth) medications that are taken at home. Patients in the VenDex arm will receive venetoclax taken by mouth once daily plus dexamethasone taken by mouth once every week for each 28-day cycle. Patients in the control arm will receive Pomalyst taken by mouth once daily on Days 1–21 for each 28-day cycle plus dexamethasone taken by mouth once every week for each 28-day cycle.

NCT02899052: This phase II, multicenter, open label, inter-

national study will compare venetoclax in combination with Kyprolis® (carfilzomib) and dexamethasone (VenKd) vs. the standard Kd treatment in 120 adult patients with t(11;14)-positive relapsed or refractory myeloma and who have received at least one prior line of therapy. This study will determine the appropriate doses to be used in the VenKd combination, and the safety and effectiveness of VenKd when compared with Kd. Patients will receive varying doses of the VenKd combination or standard treatment. Treatment consists of oral and intravenous (IV, into the vein) medications.

NCT03314181: This is a phase I/II, multicenter, international

study with three distinct parts: Part 1 is non-randomized and includes participants with t(11;14)-positive relapsed/refractory myeloma who receive increasing doses of venetoclax with fixed doses of Darzalex® (daratumumab) and dexamethasone (VenDd).

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Part 2 is non-randomized and includes participants with relapsed/refractory myeloma who will receive increasing doses of venetoclax with fixed doses of Darzalex, Velcade® (bortezomib), and dexamethasone (VenDVd). Each dose escalation phase will be followed by a single-arm, open-label expansion phase. Part 3 will include a randomized, open-label expansion phase in participants with t(11;14)-positive relapsed/refractory myeloma who will receive VenDd or DVd (Darzalex, Velcade, dexamethasone).

Treatment may consist of oral, IV, or subcutaneous (under the skin) medications. The overall objective is to evaluate the safety and efficacy of VenDd at two dose levels vs. DVd.

Potential side effects When used in leukemia and lymphoma, the most common side effects that have been observed are neutropenia (low count of neutrophils – a type of white blood cell), anemia (low count of red blood cells), thrombocytopenia (low count of platelets), diarrhea, nausea, upper respiratory tract infection, and fatigue.

Serious side effects include tumor lysis syndrome (TLS, caused by rapid destruction of cancer cells leading to accumulation of chemicals in bloodstream) and a potential to cause fertility problems in males.

Potential benefits in myeloma Venetoclax has demonstrated activity in patients with relapsed/ refractory disease who have the t(11;14) translocation. Singleagent venetoclax or venetoclax as part of a combination therapy could be a valid treatment option for this group of patients who have not responded to other standard combinations.

As published in June 2021 in the American Journal of Hematology, investigators at Mayo Clinic (Rochester, MN) reviewed the medical records of 56 patients with relapsed/refractory myeloma to study the efficacy and safety of venetoclax used outside of clinical trials at Mayo Clinic between December 2016 and March 2019. Among these patients, 75% were positive for t(11;14) translocation, 95% were refractory to an immunomodulatory agent and proteasome inhibitor, 55% had received venetoclax as monotherapy or in combination with dexamethasone, and 45% had triplet or quadruplet combination therapy. No patient experienced TLS and the overall response rate (ORR) in 52 evaluable patients was 44%. Investigators concluded that venetoclax demonstrates encouraging activity in t(11;14)-positive relapsed/ refractory myeloma.

Myeloma is in a group of disor­ders characterized by different underlying genetic abnormalities. Venetoclax for the first time offers the opportunity to personalize the treatment for a group of patients based on their disease characteristics – a first step toward precision medicine in myeloma. MT Dr. Shaji K. Kumar is a member of the IMF’s International Myeloma Working Group and a Co-Chair of its SMM Working Committee, and he is Chair of the Myeloma, Amyloidosis, Dysproteinemia Group and the Mark and Judy Mullins Professor of Hematological Malignancies at Mayo Clinic, Rochester, Minnesota. info@myeloma.org

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Special Event

IMF Honors Leaders in the Field of Myeloma Dr. Nikhil Munshi and Dr. Shaji Kumar are the recipients of the 2021 Awards by the International Myeloma Working Group

In June 2021, during the 12th Annual Summit of the International Myeloma Working Group (IMWG), Dr. Nikhil Munshi and Dr. Shaji Kumar were recognized for their excellence in myeloma research. Dr. Nikhil Munshi received the Robert A. Kyle Lifetime Achievement Award, named for the world-renowned myeloma expert and honoring those whose work has resulted in significant advances in research, treatment, and care of myeloma patients.

Dr. Shaji Kumar received the Brian G.M. Durie Outstanding Achievement Award, named for the IMF Chairman, Dr. Brian Durie, in recognition of excellence in myeloma research.

“Our honorees have continued to build on the work of Dr. Kyle, which has resulted in so many promising advances,” Dr. Durie said. “We applaud their accomplishments and important contributions to improving the lives of myeloma patients. We hope that they and their work inspire the researchers who attend the IMWG Summit to aim even higher to help us understand and ultimately find a cure for this disease.”

Robert A. Kyle Lifetime Achievement Award Dr. Nikhil Munshi is the Kraft Family Chair and Professor of Medicine at the Harvard Medical School and the Director of Basic and Correlative Science, and Associate Director of the Jerome Lipper Myeloma Center at the Dana-Farber Cancer Institute in Boston. He is an attending physician at the Brigham and Women’s Hospital.

“It is an incredible honor to receive this award named after the pioneer in myeloma and leader of clinical studies, Dr. Robert Kyle,” said Dr. Munshi. “It recognizes the contributions of many – most importantly the patients. With their help and motivation, I think a cure is on the horizon.”

Dr. Munshi’s research focuses on understanding genomic changes in myeloma and molecular mechanisms driving cancer, as well as improving diagnosis, prognosis, and therapeutics.

His clinical interests include CAR T-cell therapy and novel targeted therapeutics.

Dr. Nikhil Munshi and Dr. Robert A. Kyle

Dr. Nikhil Munshi and family

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Brian G.M. Durie Outstanding Achievement Award Dr. Shaji Kumar is a consultant in the Division of Hematology and the Mark and Judy Mullins Professor of Hematological Malignancies at Mayo Clinic in Rochester, Minnesota. He is Chair of the Myeloma, Amyloidosis, and Dysproteinemia Disease Group, and an Associate Chair for research in the Department of Medicine, Mayo Clinic.

“The myeloma community has been a second family to me, and I am deeply honored to be receiving this recognition,” said Dr. Kumar. “It has been my privilege to work with my colleagues all these years to improve the outcomes of patients with myeloma and related disorders, and I am very grateful for the opportunity to be part of this journey.”

Dr. Kumar is the principal investigator of clinical trials exploring new drugs and combinations for newly diagnosed and relapsed myeloma. His laboratory focuses on understanding the role of bone marrow microenvironment in the development and progression of myeloma.

“These two extraordinary researchers have made tremendous impacts on the diagnosis and treatment of multiple myeloma,” said Dr. Durie. “While the disease is as of yet incurable, the efforts of Dr. Munshi and Dr. Kumar are getting us closer to a cure.”

During the award presentation, Dr. Munshi and Dr. Kumar received heartfelt congratulations from their IMWG colleagues, along with celebratory photo montages of their lives. The ceremony was a resounding success even in its virtual format, but everyone is looking forward to next year’s Summit and honoring the 2020, 2021, and 2022 IMWG Award recipients in person. MT Dr. Shaji Kumar and Dr. Brian G.M. Durie

Dr. Shaji Kumar and family

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Nurse Leadership Board Kevin Brigle, PhD, NP Massey Cancer Center Virginia Commonwealth University Donna D. Catamero, ANP-BC, OCN, CCRC

Myeloma Translational Research Mount Sinai Health System Kathleen Colson, RN, BSN, BS Dana-Farber Cancer Institute Deborah Doss, RN, OCN Dana-Farber Cancer Institute Beth Faiman,

PhD, RN, MSN, APN-BC, AOCN®, FAAN

Cleveland Clinic Taussig Cancer Institute Charise Gleason,

MSN, NP-C, AOCNP®

Winship Cancer Institute of Emory University Michaela Hillengass, RN* Roswell Park Comprehensive Cancer Center *German certified

Tracy King, RN, MN Institute of Hematology Royal Prince Alfred Hospital Patricia A. Mangan, RN, MSN, APRN-BC

Abramson Cancer Center University of Pennsylvania Ann McNeill, RN, MSN, APN John Theurer Cancer Center Hackensack University Medical Center Teresa S. Miceli, RN, BSN, OCN William von Liebig Transplant Center Mayo Clinic – Rochester Kimberly Noonan, DNP, ANP-BC, AOCN®

Dana-Farber Cancer Institute Amy E. Pierre, RN, MSN, ANP-BC Memorial Sloan Kettering Cancer Center Tiffany Richards,

PhD, ANP-BC, AOCNP®

MD Anderson Cancer Center

The IMF’s NLB Turns 15!

Nurses enhance the care of myeloma patients with dedication and empathy

By Diane Moran IMF Senior Vice President, Strategic Planning

The IMF founded the Nurse Leadership Board® (NLB) in 2006 to address an unmet need in the patient and caregiver experience. The NLB is a professional partnership of nurse experts caring for myeloma patients at leading medical centers across the US. “At the inaugural meeting of NLB members in 2006 in Dallas, Texas, we couldn’t even conceive of all that the NLB would become,” recalls founding member Beth Faiman. “The NLB is unique – there is nothing else like it.”

The NLB remains at the forefront of myeloma care.

“We regularly lead discussions with patients and nurses, and dive deeply into topics in order to understand the current perceptions and unmet needs,” says Teresa Micelli, who co-moderated a recent discussion session. “This understanding helps us identify and prioritize activities like teleconferences, publications, and other materials that the IMF and the NLB create to help patients and caregivers.”

The nurses of the NLB are a “golden thread” woven into the beautiful fabric of vast programs of the IMF. They possess an extraordinary blend of scientific insight and an understanding of patients and caregivers. The NLB nurses make everything they touch amazing, from the IMF Patient & Family Seminars and Regional Community Workshops, to publications like the IMF tip cards and Understanding-series brochures, Living Well with Myeloma teleconferences, and more.

Recent discussions included treatment decision-making among an increasing number of available options, CAR T-cell therapy, the unique side effects of new treatments, as well as disparities in myeloma treatments and outcomes. Both patients and nurses are enthusiastic participants in these discussions and appreciate the opportunity to have their opinions heard.

The NLB’s mission to enhance the nursing care and self-care of patients with myeloma has remained unchanged, but the activities the group has undertaken have evolved over time. In 2006, the NLB produced the first of its consensus guidelines for side effect management in response to drugs that were newly available at that time, Velcade® (bortezomib) and Revlimid® (lenalidomide). The NLB has continued to enhance nursing education about myeloma through a popular symposium at the Oncology Nursing Society annual meeting. In recent years, the addition of international members has broadened the scope of the NLB beyond the US.

Such discussions contributed to educational outreach and the development of a new tool and accompanying video to enhance treatment decision-making and help patients and caregivers get the most from their office visit, and support a dialogue with their healthcare providers.

With dedication and empathy, the nurses of the NLB will continue to enhance the nursing care and self-care of patients with myeloma for many, many years to come. MT

Visit nlb.myeloma.org to learn how the NLB is improving the nursing care and self-care of patients with myeloma via consensus publications, symposia, multimedia, and research.The Myeloma Treatment Discussion Tool created by the NLB is avail­ able through the IMF by calling 800.452.CURE in the US and Canada or 818.487.7455 worldwide, or by emailing TheIMF@myeloma.org.

Sandra I. Rome,

RN, MN, AOCN®, CNS

Cedars-Sinai Medical Center Mary Steinbach, DNP, APRN Huntsman Cancer Institute University of Utah Joseph D. Tariman,

PhD, RN, ANP-BC, FAAN

College of Science and Health De Paul University Daniel Verina,

DNP, RN, ACNP-BC

Mount Sinai Medical Center

NLB members at the 2019 annual meeting in Hoboken, New Jersey

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info@myeloma.org

myeloma.org

Resources

Quarterly Resource Updates Fast click-through weblinks!

covid19.myeloma.org

videos.myeloma.org

¡ One-stop resource for the latest information on COVID-19 and vaccination for myeloma patients

inclusion.myeloma.org Brian G.M. Durie, MD

Thomas Martin, MD

María-Victoria Mateos, MD

Nikhil Munshi, MD

¡ 2021 ASCO & EHA: What Patients & Caregivers Need to Know

¡ At mpower.myeloma.org you will learn how we are turning the vision of inclusion into a reality. ¡ What are some disparities in the treatment and care of patients with myeloma? ¡ How is myeloma different in African Americans?

infoline.myeloma.org

¡ 2021 IMWG Conference Series: Making Sense of Treatment ¡ Ask Dr. Durie: What can myeloma patients do to strengthen their immune system? ¡ Living Well with Myeloma: Financial & Other Resources for Patients & Caregivers ¡ IMF Virtual Regional Community Workshop

publications.myeloma.org

¡ Contact the IMF InfoLine with your myeloma-related questions and concerns at InfoLine@myeloma.org ¡ At medications.myeloma.org you will find info on FDA-approved myeloma therapies ¡ At resources.myeloma.org you may find reimburse­ment and co-pay assistance programs ¡ support.myeloma.org or rtuohy@myeloma.org will help you find a myeloma support group

¡ Booklets that explain myeloma therapies and more ¡ Tip cards on topics important to myeloma patients ¡ Guide to Myeloma Acronyms and Abbreviations ¡ Guide to Myeloma Terms and Definitions ¡ Myeloma Today, Spring 2021 edition

Check back often at myeloma.org as the IMF website is continually updated.

Sign up at subscribe.myeloma.org to receive alerts about IMF events, webinars, teleconferences, and advocacy actions, as well as the IMF e-newsletter Myeloma Minute. And engage with us on social media!

facebook.com/myeloma

twitter.com/IMFmyeloma

800.452.CURE toll-free in USA and Canada

818.487.7455 worldwide

instagram.com/IMFmyeloma

youtube.com/IMFmyeloma

SUMMER 2021

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Advocacy

IMF Hosts the Second Annual Meeting of the “All Cancers Congress” 17 cancer advocacy organizations share insights and legislative priorities

By Robin Levy IMF Senior Director, Public Policy & Advocacy

On May 13, 2021, the International Myeloma Foundation’s Advocacy team hosted the second annual meeting of the All Cancers Congress (ACC). The ACC was developed and is coordinated by the IMF to bring together advocacy organizations that are focused on helping patients with cancer, and who operate within the federal policy and regulatory space. Too often, cancer advocacy organizations work on projects and set goals without the support or knowledge of outside groups, and become aware of a new program or policy push by like-minded organizations only after an initiative is already underway. The goal of the ACC is to break this “silo” model and establish an open venue for cancer advocacy groups to share resources, insights, and legislative priorities in order to enhance our efforts on the behalf of the patients we serve.

Seventeen different cancer advocacy groups were represented at the second annual meeting of the ACC. Each group shared their successes and challenges, advocacy efforts, and legislative priorities for 2021 with the goal of finding opportunities to foster collaboration among ACC members. Topics deliberated upon most heavily included equality of access and care disparities. Advocacy group representatives discussed how they plan to engage policy makers about these issues more effectively.

The ACC meeting was initially conceived as a yearly event, but the COVID-19 pandemic brought with it a realization for ACC members that the cancer patient community would face specific

SUPPORT FOR VETERANS Get Your VAM Guide to VA Benefits

needs and challenges, and so they immediately began meeting on a weekly basis. The meetings during the ongoing pandemic have been utilized to ensure that the voices of cancer patients are being heard on important issues such as access and triaging of care, and vaccine distribution and telehealth.

The pandemic has also increased awareness of inequities in care experienced by racial and ethnic minorities, as well as individuals who face issues due to their socioeconomic status, and those who reside in rural areas.

Letters were written to state governors on issues such as expanding the 90-day supply of prescription medications as recommended by the Centers for Disease Control and Prevention (CDC) and pandemic plans. We invite you to visit the coalition’s new website allcancerscongress.org where you can read and download the ACC 90-day supply letter, the vaccine letter, and the triage letter. MT

To follow the IMF’s broader advocacy activities, please visit advocacy.myeloma.org, subscribe to the IMF Advocacy Newsletter at subscribe.myeloma.org, and contact our team at advocacy@myeloma.org. We welcome your engagement, questions, and ideas.

The Veterans Against Myeloma (VAM) Guide to VA Benefits assembles information from various resources into one cohesive narrative specific to myeloma. This VAM Guide is intended to help Veterans with myeloma, their caregivers, and family members to navigate the VA claims process, myeloma service connections, understanding authoritative bodies, and VA claim appeals.

YOU ARE NOT ALONE. THE IMF IS HERE TO HELP. VETERANS.MYELOMA.ORG

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info@myeloma.org

myeloma.org

Philanthropy

Investing in the Future

YOU could help advance the methods to find a cure for myeloma

By Lynn K. Green, Ed.D IMF Senior Vice President, Philanthropy

Each year, the number of people diagnosed with multiple myeloma continues to grow. At the same time, our understanding of this disease continues to deepen. Over the course of the past decade, there have been significant scientific and clinical advances in the field of myeloma, which have improved patient outcomes. With new drugs, new drug classes, and new combination therapy protocols approved by the US Food and Drug Administration (FDA), patients are living better and living longer. However, most myeloma patients will eventually become resistant to treatment and experience a relapse. Members of the IMF’s International Myeloma Working Group, who conduct collaborative research to improve outcomes for myeloma patients, believe that early detection can prevent the progression to active myeloma.

We are learning more and more about the genetic and molecular mechanisms of resistance to current therapies. The BSRI team and other researchers are studying aspects of the myeloma microenvironment to assess possible solutions.

The good news is that even patients with higher-risk myeloma can achieve better outcomes if MRD-negative status is achieved.

The IMF’s BSRI approach is bringing a level of optimism for all patients, but we need your help to reach the finish line.

YOU could become a critical driver to help ensure that the next breakthroughs in treatment are made by making a philanthropic contribution today.

Join us in finding the cure for myeloma! MT

In 2012, the IMF established the Black Swan Research Initiative® (BSRI®) with the sole purpose of searching for a cure. In 2018, the IMF launched the first “CURE” clinical trial in the United States. The ASCENT (Aggressive Smoldering Curative Approach Evaluating Novel Therapies) clinical trial evaluates the use of prominent myeloma drug combinations in patients with highrisk smoldering multiple myeloma (HR SMM). The presence of a precursor phase of SMM, and the ability to identify patients at the highest risk of progression, leads us to believe that we can cure the disease through early intervention.

Nearly fully enrolled, the ASCENT clinical trial combines four drugs approved by the FDA for the treatment of myeloma: Kyprolis® (carfilzomib), Revlimid® (lenalidomide), Darzalex® (daratumumab), and the steroid dexamethasone. Minimal residual disease (MRD) is assessed at each treatment phase and post-treatment. MRD refers to the number of myeloma cells that remain in the patient after treatment. A patient who tests MRD-negative has less than one myeloma cell per million bone marrow cells – meaning that no myeloma cells are detected.

Great progress has been made. Many patients in the ASCENT clinical trial are achieving MRD-negative status. It is anticipated that approximately 80% of myeloma patients in the ASCENT clinical trial will achieve MRD-negativity. The next step is to establish if this MRD-negative status is sustained long-term at 1 year, 3 years, 5 years, and beyond. Myeloma patients who remain MRD-negative suggest an exceptional probability that the patient is cured!

As we witness the successes in the ASCENT clinical trial, the IMF is already setting up the next series of important studies to push to more sustained MRD-negativity. These studies will include investigations of CAR T-cell therapies as well as bi-specific antibodies in MRD-positive patients, and ultra-high-risk SMM. 800.452.CURE toll-free in USA and Canada

818.487.7455 worldwide

PARTNERS PARTNERS IN PROGRESS IN PROGRESS

Supporting Myeloma Research Toward a Cure The IMF is improving the outcomes of myeloma patients, and moving towards a cure. With clinicians and researchers from top institutions around the world working together, the IMF is taking the first steps to The IMF is improving the outcomes myeloma patients, identifying curative treatments in subsets ofof patients.

With dedicated support, you toward can helpathe IMFWith change the trajectory of myeloma. and moving cure. clinicians and researchers

Supporting Myeloma Research Toward a Cure

from top institutions around world working together, If you would like to learn how tothe partner with us, please contact: the IMF is taking steps to identify curative treatments in Lynn K. Green, Ed.D. Brenda Hawkes subsets ofPresident, patients.

With philanthropic support, you can Senior Vice Philanthropy Senior Director, Philanthropy 334.332.0888 870.403.2251 help the IMF change the trajectory of myeloma. If you lgreen@myeloma.org bhawkes@myeloma.org would like to learn how to partner with use, please contact:

Lynn K. Green, Ed.D. Senior Vice President, Philanthropy TOGETHER WE CAN MAKE “MYELOMA HISTORY!” 334.332.0888 • lgreen@myeloma.org TOGETHER WE CAN MAKE MYELOMA HISTORY! SUMMER 2021

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ASCO & EHA 2021 – CONTINUED FROM PAGE 4 myeloma. Of the many important myeloma-related abstracts presented at EHA, there is one that requires its own discussion.

MAIA clinical trial follow-up The primary analyses of phase III clinical trials – ALCYONE, MAIA, CASSIOPEIA – have established the superior efficacy of Darzalex in combination with standard-of-care regimens vs. standard-of-care alone for patients with newly diagnosed myeloma. After long follow-up, ALCYONE data showed an OS benefit when adding Darzalex to Velcade + melphalan + prednisone. In the primary analysis of data from the MAIA study, D-Rd (Darzalex + Revlimid + dexamethasone) reduced the risk of disease progression or death by 44% when compared to Rd alone.

After almost 5 years of follow-up in transplant-ineligible patients, a significant and clinically meaningful OS improvement of 66.3% was demonstrated with D-Rd vs. 53.1% with Rd, representing a 32% reduction in the risk of death. This means that more than two thirds of patients in the D-Rd arm were alive at 5 years. The significant PFS benefit of D-Rd vs. Rd from the primary analysis was maintained – at 5 years, over 50% of patients in the D-Rd arm were still in remission! These results, together with the OS benefit observed in ALCYONE, support the use of frontline Darzalex-based regimens for optimal long-term outcomes.

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SUMMER 2021

The 2021 ASCO and EHA meetings were quite exciting. I strongly encourage you to visit videos.myeloma.org and click on the “ASCO/EHA” tab to view the webinar by Dr. Brian G.M. Durie, Best of 2021 ASCO & EHA: What Patients & Caregivers Need to Know, as well as the more than 40 fascinating interviews by the IMF with the top myeloma researchers who presented their data at the 2021 ASCO and EHA meetings. MT

The International Myeloma Foundation presents

BEST OF 2021 ASCO & EHA

What Patients and Caregivers need to know Webinar by Brian G.M. Durie, MD IMF Chairman of the Board Duration: 60 minutes (including Q&A)

Go to videos.myeloma.org and click on the “ASCO/EHA” tab to view the recording of this recent webinar.

info@myeloma.org

myeloma.org

800.452.CURE toll-free in USA and Canada

818.487.7455 worldwide

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International Myeloma Foundation 12650 Riverside Drive, Suite 206 North Hollywood, CA 91607-3421 USA myeloma.org 800.452.CURE

Printed in USA © 2021 International Myeloma Foundation. All rights reserved.

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Dedicated to improving the quality of life of myeloma patients while working toward prevention and a cure.

2021 IMF Calendar of Events Aug 7

IMF Regional Community Workshop – virtual

Oct 2 IMF Regional Community Workshop – virtual

Aug 12

Living Well with Myeloma: Financial & Other Resources for Patients and Caregivers – virtual

Oct 9 IMF Regional Community Workshop – virtual

Aug 14

IMF Patient & Family Seminar – virtual

Oct 30

IMF Patient & Family Seminar – virtual

Oct 23-24 Asian Myeloma Network (AMN) Annual Summit – virtual

Aug 25-26 Global Myeloma Action Network (GMAN) Annual Summit – virtual

Nov 6 IMF Regional Community Workshop – virtual

Aug 28

IMF Regional Community Workshop – virtual

Nov 13

IMF M-Power Community Workshop – Atlanta, GA – virtual

Sept 4

IMF Patient & Family Seminar – virtual

Nov 20

IMF Regional Community Workshop – virtual

Sept 8-11 18th International Myeloma Workshop (IMW) – Vienna, Austria Sept 25 IMF M-Power Community Workshop – Baltimore, MD – virtual

Dec 10-14 63rd Annual Meeting and Exposition of the American Society of Hematology (ASH) – Atlanta, Georgia

Visit events.myeloma.org for the latest information about upcoming activities.

For information about international activities by IMF affiliates, please visit these websites:

Australia

myeloma.org.au

Canada

myelomacanada.ca

Israel

amen.org.il

Japan

myeloma.gr.jp

Latin America

mielomabrasil.org