EHA Highlights

Hematologi EHA 2021

Held on 10-13 June, EHA 2021 virtual congress provided new insights from the world of hematology. We at BestPractice Nordic had an opportunity to meet virtually some of the leading scientists within hematology, who presented research findings at EHA.

Dr. Agoston Gyula Szabo of our Scientific Advisory Board put forward questions regarding each study from the Nordic perspective. See the highlights below and hear the answers on bpno.no.

Data from the MonumentTAL-1 study Dr. Amrita Y. Krishnan presented an update on phase I data from the MonumentTAL-1 study on the safety, tolerability and efficacy of the recommended phase II dose (RP2D) of talquetamab in patients with relapsed and refractory multiple myeloma.

Talquetamab is a first-in-class bispecific immunoglobulin G4 antibody that binds to CD3 and GPRC5D to activate T cells to attack multiple myeloma cells. The study has shown a high clinical response rate in patients with relapsed and refractory multiple myeloma.

In our MEDtalk Dr. Krishnan answers the following questions: • The response rates reported here are very impressive. Do you think responses will be durable? What is your impression? • Is there any aspect of talquetamab treatment that is problematic for patients? Any significant hair or nail issues? • If you could choose, where would you position talquetamab in the sequence of myeloma treatments for your patient?

Dr. Amrita Y. Krishnan, Director of Judy and Bernard Briskin Multiple Myeloma Center, Professor of Hematology/Hematopoietic Cell Transplantation, City of Hope Cancer Center

– highlights

Teclistamab demonstrates encouraging efficacy Dr. Niels W.C.J. van de Donk presented updated results from the first-in-human phase 1 study of teclistamab in patients with relapsed/refractory MM who were treated at the recommended phase 2 dose (RP2D). Teclistamab is a bispecific immunoglobulin G4 antibody that binds to both BCMA and CD3 to redirect CD3+ T cells to BCMA-expressing multiple myeloma cells.

The results showed that teclistamab was well tolerated at the weekly RP2D of 1500 μg/kg SC and demonstrated encouraging efficacy with durable, deepening responses.

In the MEDtalk Dr. van de Donk offers his perspective on the following questions: • Teclistamab seems like one of the most effective therapies for relapsed and refractory myeloma. When do you think we can offer this treatment for our patients in Europe? • A number of trials incorporating teclistamab in the current treatment algorithm of myeloma are underway. Where would you position this drug if you could decide? First line? Relapse? Upfront? Instead of highdose melpahan? Consolidation? Maintenance? • Besides teclistamab, several other classes of BCMAtargeted therapies are emerging, like antibody-drugconjugates and CAR-Ts. We could assume that one

BCMA therapy will worsen the efficacy of the others, which means that these drugs compete for a place in myeloma. Which BCMA therapy do you see as the winner?

Dr. Niels W. C. J. van de Donk, Department of Hematology, VU University Medical Center, Amsterdam, The Netherlands

Dr. Mounzer Agha, MD, director of the Mario Lemieux Center for Blood Cancers at UPMC Hillman Cancer Center

Examination of CAR-T cell therapy for outpatient treatment CARTITUDE-2 is a multicohort, phase II study to evaluate the safety and efficacy of Cilta-cel in different clinical settings for patients with multiple myeloma and examines whether the drug is suitable for outpatient administration. Dr. Mounzer Agha concluded that a single Cilta-cel infusion at the recommended phase 2 dose gave an early and deep response with manageable side effects in patients with multiple myeloma who had received 1-3 prior treatments. In the future it will be possible to conclude whether outpatient treatment is possible.

Dr. Agha illuminates the future possibilities of CAR-T cell therapy while answering the following questions: • The reported response rates in the CARTITUDE-2 study are very impressive. Can you comment on the durability of response? • Could you report how much time elapsed from T-cell collection to CAR-T infusion? • We are looking forward to Cilta-cel soon becoming the second approved treatment modality in CAR-T therapy for myeloma. Could you name significant differences regarding the dosing administration of

Cilta-cel in comparison with Bluebirds ide-cel? • The patients reported on in this abstract were not so heavily pretreated as we have seen with other

CAR-T cells. Do you think the Cilta-cel will have a place in the «early» relapse treatment of myeloma?

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– highlights

Addition of daratumumab reduces risk of death In a late-breaking study Dr. Thierry Facon and Dr. Torben Plesner presented 5-year data from the MAIA study, which shows that the addition of daratumumab to lenalidomide and dexamethasone significantly reduced the risk of death in patients with newly diagnosed multiple myeloma where transplantation is not possible. The risk of death was reduced by 32% compared with lenalidomide and dexamethasone alone.

The clinical benefit of the primary analysis of the MAIA study was maintained at 5-year follow-up and the benefit of upfront D-Rd given until progression was confirmed with a survival benefit, which further supports the use of upfront daratumumab as a new standard for patients who are not eligible for transplantation.

We talked to two authors of the study: Dr. Torben Plesner introduced the study and Dr. Thierry Facon provided answers to the following questions: • Is daratumumab-lenalidomide-dexamethasone the best therapy in the history of multiple myeloma? • Will it be a problem for approvals that we do not have a head-to-head comparison with VRD? • Although the dara-len-dex regimen is very well tolerated in the elderly, some discontinue lenalidomide and continue daratumumab «maintenance».

This is still very effective, as seen in the ALCYONE study. Can you tell us the (approximate) percentage of patients in the intention-to-treat daratumumab arm that discontinued lenalidomide? • Hopefully dara-len-dex will soon be approved across

Europe for the benefit of elderly patients with myeloma. But what should we do when this regimen fails?

Which options would you consider in an 83-yearold patient who progresses after five years of continuous dara-len-dex and has become a little frail in the meantime? Do we have anything «good» that does not require at least weekly visits?

Dr. Torben Plesner, Clinical Professor, IRS, Lillebælt Hospital, Hematology.

MEDtalk HIGHLIGHTS

Thierry Facon

Potential to become the best treatment for multiple myeloma in history

Flere interessante kliniske data for brentuximab vedotin til patienter med Hodgkin lymfom

Fedratinib improves OS and PFS for patients with myelofibrosis as first-line therapy and after ruxolitinib

Martin Hutchings

Claire Harrison

EHA-ESMO

EHA-ESMO Clinical Practice Guidelines for MM Multiple myeloma: EHA-ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up were published earlier this year. Dr. Fredrik Schjesvold was one of the nominated authors to write the Guidelines. Dr. Schjesvord introduces us to the Guidelines in a MEDtalk video.

The Guidelines were developed by the European Hematology Association (EHA) and European Society for Medical Oncology (ESMO) and approved by the EHA Board and the ESMO Guidelines Committee in November 2020. • The Guidelines provide key recommendations on the management ofmultiple myeloma. • Key treatment recommendationsareprovided for both newly diagnosed myeloma patients and patients with relapsed/refractory disease. • Recommendations for the treatment of plasma cell leukaemia, solitary plasmacytoma and smouldering myeloma are also provided. • Key recommendations for myeloma complications, including bone disease and renal impairment, are included.

Fredrik Schjesvold, Leader of Oslo Myeloma Center, Oslo University Hospital and K.G. Jebsen Centre for B Cell Malignancie, University of Oslo

Read more: Dimopoulos MA, Moreau P, Terpos E. Multiple myeloma: EHA-ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2021;32(3): 309-322. DOI:10.1016/j.annonc.2020.11.014