Highlights from the EBMT 2021 virtual meeting

Teclistamab in relapsed/refractory multiple myeloma

Teclistamab is a bispecific antibody therapy that is currently being trialled for the treatment of relapsed/refractory myeloma. Teclistamab targets both B-cell maturation antigen (BCMA) and CD3 on T-cells to induce T-cell mediated killing.

In this video, Saad Usmani, MD, MBBS, MBA, of the Levine Cancer Institute and Atrium Health in Charlotte, NC, gives an overview of the findings of a Phase I/II dose-escalation trial (NCT04557098) of teclistamab in patients with relapsed/refractory myeloma, comparing results for subcutaneous and intravenous delivery.

Prof. Usmani reports that subcutaneous delivery of teclistamab achieved an overall response rate of 73% in patients with relapsed/refractory myeloma with 75% of responders being penta-refractory. The median time to response was one month.

Cytokine release syndrome (CRS) was observed in 55% of patients overall and in 64% of patients receiving the recommended Phase II dose of 1500 µg/kg delivered subcutaneously. All cases of CRS were reported as grade I or II and did not result in discontinuation of treatment.

Prof. Usmani concludes that teclistamab appears to be well-tolerated and effective in the treatment of multiple myeloma and is now moving forward into an expansion cohort.

Post-transplant maintenance for patients with AML

Relapse rates for patients with acute myeloid leukemia (AML) who undergo hematopoietic stem cell transplantation (HSCT) remain high and present an unmet medical need. In this video, Ali Bazarbachi, MD, PhD, of the American University of Beirut Medical Center in Lebanon discusses mitigation strategies to reduce the risk of relapse.

For patients treated with hypomethylating agents, Dr Bazarbachi highlights a potential reduction in relapse rate. Results of a Phase II trial have indicated that low-dose azacitidine may prolong leukemia-free survival in patients with AML post-HSCT.

FLT3-ITD is one of the most common mutations in patients with AML and is associated with a high rate of relapse. Dr Bazarbachi reports that using FLT3 inhibitors such as sorafenib post-relapse can reduce the rate of relapse.

Overall, these studies demonstrate promising results for patients with AML who are undergoing HSCT.

Novel scoring system defines allo-HSCT patients at high risk for CMV

Ibrahim Yakoub-Agha of the University of Lille in France outlines the development of a novel scoring system for patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) to identify those who are at high risk of cytomegalovirus (CMV) infection.

The treatment of CMV can have severe side effects including cytopenia and renal impairment. As such, a prognostic scoring system has been developed which can assess the value of CMV prophylaxis for individuals, based on an individual risk score.

Prof. Yakoub-Agha describes how a retrospective analysis of data from 3690 patients who underwent allo-HSCT was used to develop this prognostic scoring system which incorporates factors including having a CMV-seropositive donor, having an unrelated donor, antithymocyte globulin, myeloablative conditioning, total body irradiation and mycophenolate mofetil, to calculate risk.¹

Monoclonal antibodies for relapse post-ASCT in myeloma

Mohamad Mohty of the Saint-Antoine Hospital in Paris, France, outlines the use of monoclonal antibodies for the treatment of multiple myeloma relapsed after autologous stem cell transplantation (ASCT), highlighting key clinical trials.

ASCT is the standard of care for patients with myeloma who are eligible, however, it is not curative and patients will eventually relapse. Many novel therapies are being investigated for treatment after first relapse, including the monoclonal antibody therapies daratumumab and isatuximab, both of which target CD38.

Lenalidomide is an immunomodulatory drug which is used as maintenance therapy in patients with multiple myeloma. Prof. Mohty discusses the need for different treatment strategies for lenalidomide-refractory and lenalidomide-sensitive patients when using monoclonal antibodies.

For patients who are lenalidomide-sensitive, Prof. Mohty outlines the use of daratumumab plus lenalidomide and dexamethasone which has shown promising results in the POLLUX trial (NCT02076009).²

Prof. Mohty also indicates the option to use a monoclonal antibody therapy in combination with an immunomodulatory drug, drawing attention to the APOLLO trial (NCT03180736) of daratumumab plus pomalidomide and dexamethasone, and the ICARIA-MM trial (NCT02990338) of isatuximab plus pomalidomide and dexamethasone.³

Haploidentical versus unrelated transplant in ALL

Access to an appropriate donor is a critical element of success for the treatment of relapsed acute lymphocytic leukemia (ALL). HLA-matched sibling donors are preferred; however, these are only available for a small proportion of patients.⁴

HLA-matched unrelated donors can achieve similar outcomes to HLA-matched sibling donors but can take a long time to find. Haploidentical stem cell transplantation uses donors who are half-matched to the recipient and can be used when HLA-matched sibling donors and HLA-matched unrelated donors are not available.⁵

In this video, Arnon Nagler of the Chaim Sheba Medical Center in Tel-Hashomer, Israel, outlines research comparing the outcomes of patients with ALL who receive haploidentical versus unrelated transplantation.

Prof. Nagler reports that haploidentical transplantation achieves similar results compared to HLA-matched and HLA-mismatched unrelated transplantation. Further comparison of haploidentical versus sibling transplantation has reported similar results in terms of leukemia-free survival, overall survival and GvHD relapse-free survival. Prof. Nagler also highlights a lower relapse rate for haploidentical transplant.

CAR-T moving forwards for R/R DLBCL

Anna Sureda of the Catalan Institute of Oncology in Barcelona, Spain discusses the role of stem cell transplantation and the use of chimeric antigen receptor T-cell (CAR-T) therapy for the treatment of diffuse large B-cell lymphoma (DLBCL).

Two CAR-T therapies have received FDA approval for the treatment of DLBCL so far. Axicabtagene ciloleucel is currently approved for the treatment of adults with DLBCL who have received two or more prior lines of systemic therapy. This approval was based on results of the ZUMA-1 trial (NCT02348216) which reported a 51% complete remission rate (95% CI: 41, 62) with the median duration of response not reached (95% CI: 8.1 months, not estimable) at a median of 7.9 months of follow-up⁶.

Lisocabtagene maraleucel is also approved for the treatment of adults with DLBCL who have received two or more lines of systemic therapy. Approval of lisocabtagene maraleucel was based on results of the TRANSCEND-NHL-001 trial (NCT02631044) which achieved a 54% complete response rate (95% CI: 47, 61), with 62% of patients having a remission lasting at least nine months⁷.

Dr Sureda gives an overview of how CAR-T therapies are impacting the treatment of DLBCL, highlighting their potential to be used in earlier phases of treatment, pending the results of ongoing trials.

References

Beauvais, D., Drumez, E., Blaise, D., et al, Scoring system for clinically significant CMV infection in seropositive recipients following allogenic hematopoietic cell transplant: an SFGM-TC study, Bone Marrow Transplantation. December 2020, DOI: 10.1038/s41409-020-01178-6
Matoes, M-V., Spencer, A., Nooka, A. K., et al, Daratumumab-based regimens are highly effective and well tolerated in relapsed or refractory multiple myeloma regardless of patient age: subgroup analysis of the phase 3 CASTOR and POLLUX studies, Haematoligica. January 2020; 105(2);468-477
Attal, M., Richardson, P. G., Rajkumar, S. V., et al, Isatuximab plus pomalidomide and low-dose dexamethasone versus pomalidomide and low-dose dexamethasone in patients with relapsed and refractory multiple myeloma (ICARIA-MM): a randomised, multicentre, open-label, phase 3 study, The Lancet. December 2019; 394(10214):2096-2107
Al Malki, M. M., Yang, D., Labopin, M., et al, Comparing transplant outcomes in ALL patients after haploidentical with PTCy or matched unrelated donor transplantation, Blood Advances. May 2020; 4(9);2073-2083
Ma, L., Han, X., Jiang, S., et al, Haploidentical stem cell transplantation vs matched unrelated donor transplantation in adults with hematologic malignancies: a systematic review and meta-analysis, Hematology. December 2020; 25(1);356-365
US Food & Drug Administration, FDA approves axicabtagene ciloleucel for large B-cell lymphoma. Available from: https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-axicabtagene-ciloleucel-large-b-cell-lymphoma. US Food & Drug Administration. (Last accessed 16/04/2021)
US Food & Drug Administration, FDA approves lisocabtagene maraleucel for relapsed or refractory large B-cell lymphoma. Available from: https://www.fda.gov/drugs/drug-approvals-and-databases/fda-approves-lisocabtagene-maraleucel-relapsed-or-refractory-large-b-cell-lymphoma. US Food & Drug Administration. (Last accessed 16/04/2021)