The Efficacy of Teclistamab in Multiple Myeloma Patients with Secondary Plasma Cell Leukemia

Introduction:

Teclistamab (Tec) is a B cell maturation antigen (BCMA) targeting bispecific antibody that has shown unprecedented efficacy in relapsed/refractory multiple myeloma (MM). Patients with secondary plasma cell leukemia (sPCL), a rare and highly aggressive form of relapsed/refractory MM have dismal outcomes and were excluded from the MajesTEC-1 (cite) which led to the approval of Tec. The efficacy of Tec in patients with sPCL remains largely unknown. We present the outcome of 11 patients with sPCL who received teclistamab in a real world multi-institutional cohort.

Methods:

Patients with at least 3 lines of therapy, who presented with sPCL (≥5% circulating plasma cells) at the time of step-up dosing of teclistamab at 3 academic centers in the US (University of Arkansas for Medical Sciences, Medical College of Wisconsin and Rutgers Cancer Institute) were included in this retrospective study. Various data including patient demographics, disease and treatment characteristics at the most recent assessment before initiating Tec treatment were collected and clinical outcomes, including response rates, progression free (PFS) and overall survival (OS) were analyzed.

Results:

A total of 11 patients with sPCL at the time of Tec initiation were included. The median percentage of circulating plasma cells was 6.2% (range 5.3 to 82%). All patients were triple class refractory, and 8/11 (72%) were penta-refractory. The median age was 68 years (range: 54-89), with 4/11 (36%) being male; 9/11 (82%) were Caucasians and 2/11 (18%) were African American. High risk cytogenetics including translocations t(4;14), t(14;16), deletion 17p and duplication 1q were observed in 91% of patients (n=10) and 3 (27%) patients had developed soft tissue extramedullary disease in addition to the sPCL. The median number of prior lines of therapy was 5 (range: 3-10), and 82% (n=9) had received a prior autologous stem cell transplant. Cytokine release syndrome (CRS) grade 1/2 was observed in 6/11 (55%) patients, and 5 (83%) of those received tocilizumab. No CRS grade 3/4 and no immune effector cell-associated neurotoxicity syndrome (ICANS) were observed. Overall response rate was 36% (4/11) and the best achieved response in this cohort of patients was a partial response (PR). The median time to best response was 2 months (0.6-4 months). With a median follow up of 5 months, the median PFS (mPFS) for all patients was only 19 days. This was mainly driven by non-responders, whose mPFS was 12 days, while patients who had achieved a PR had a mPFS of 4.8 months. The median OS for non-responders was 1.2 months, while the median OS for patients who achieved a PR was not reached. As the efficacy of Tec is T cell dependent, we further looked at the absolute lymphocyte count (ALC) as a predictor for response in sPCL but did not find a significant difference between responders (median=0.35x103/mL; range 0.2-1.3x103/mL) and non-responders (median=0.9x103/mL; range 0.3-1.6x103/mL), p=0.24.

Conclusion:

In this case series we show that the efficacy of Tec in patients who developed sPCL was limited with no patient achieving a VGPR or better and PFS/OS being shorter to what has been reported in clinical trials or real world data in refractory MM patients without sPCL. While the reasons for this poor outcome in sPCL are not clear, it appears that alternative treatment approaches for this poor risk patient population should be explored and studied.

Dhakal:Acrellx: Research Funding; Bristol Myers Squibb: Honoraria, Research Funding; Genentech: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria, Speakers Bureau; Sanofi: Research Funding; Karyopharm: Honoraria, Speakers Bureau; C4 therapeutics: Research Funding; Carsgen: Research Funding; Janssen: Honoraria, Research Funding, Speakers Bureau; Medical College of Wisconsin: Current Employment. Zangari:Karyopharm: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen Pharmaceuticals, Inc: Consultancy, Membership on an entity's Board of Directors or advisory committees. Al Hadidi:Sanofi: Consultancy; Pfizer: Consultancy; Janssen: Consultancy. Lentzsch:Janssen: Consultancy; Caelum Bioscience: Patents & Royalties; Poseida: Current holder of stock options in a privately-held company; Adaptive: Consultancy; Sanofi: Research Funding; GSK: Consultancy; Sanofi: Consultancy; Aptitude: Speakers Bureau; Angitia: Consultancy; Regeneron: Consultancy; Clinical Care Options (COO): Speakers Bureau; Magenta: Current holder of stock options in a privately-held company; Bio Ascend: Speakers Bureau; Alexion: Consultancy; Pfizer: Consultancy; BMS: Consultancy; Karyopharm: Consultancy; RedMed: Speakers Bureau; Takeda: Consultancy; Zentalis: Research Funding; Medscape: Speakers Bureau; Peerview: Speakers Bureau. van Rhee:Adicet Bio: Membership on an entity's Board of Directors or advisory committees; GlaxoSmithKline: Consultancy, Membership on an entity's Board of Directors or advisory committees; Karyopharm: Consultancy, Membership on an entity's Board of Directors or advisory committees; EUSA Pharma: Consultancy, Membership on an entity's Board of Directors or advisory committees; Takeda: Consultancy; Kite Pharma: Membership on an entity's Board of Directors or advisory committees; Janssen Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Secura Bio: Membership on an entity's Board of Directors or advisory committees; Castleman Disease Collaborative Network: Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb: Research Funding. D'Souza:Novartis: Research Funding; Kedrion: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Abbvie: Research Funding; Caelum: Research Funding; Bristol Myers Squibb: Consultancy, Membership on an entity's Board of Directors or advisory committees; Prothena: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Regeneron: Research Funding; Takeda: Research Funding. Chakraborty:Janssen: Consultancy; Sanofi: Consultancy; Adaptive: Consultancy. Shah:Janssen: Consultancy, Honoraria, Research Funding; Regeneron Pharmaceuticals, Inc.: Honoraria, Research Funding; Bristol Myers Squibb: Consultancy, Research Funding; Targeted Oncology: Consultancy; Dedham Group: Honoraria. Mohan:Janssen: Consultancy; Pfizer: Consultancy; Legend biotech: Consultancy; Sanofi: Consultancy, Research Funding, Speakers Bureau; BMS: Consultancy. Schinke:Arcellx: Consultancy; Janssen: Consultancy, Honoraria, Speakers Bureau; Pfizer: Consultancy, Honoraria, Speakers Bureau; Cancer Network: Honoraria; OncLive: Honoraria.