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. 2022 Sep 30;3(4):1270-1276.
doi: 10.1002/jha2.572. eCollection 2022 Nov.

Selinexor-based regimens in patients with multiple myeloma after prior anti-B-cell maturation antigen treatment

Muhamed Baljevic  1 , Cristina Gasparetto  2 , Gary J Schiller  3 , Sascha A Tuchman  4 , Natalie S Callander  5 , Suzanne Lentzsch  6 , Jorge Monge  7 , Rami Kotb  8 , Nizar J Bahlis  9 , Darrell White  10 , Christine I Chen  11 , Heather J Sutherland  12 , Sumit Madan  13 , Richard LeBlanc  14 , Michael Sebag  15 , Christopher P Venner  16 , William I Bensinger  17 , Noa Biran  18 , Andrew DeCastro  19 , Dane R Van Domelen  19 , Chris Zhang  19 , Jatin J Shah  19 , Sharon Shacham  19 , Michael G Kauffman  19 , Ohad S Bentur  19 , Brea Lipe  20
Affiliations

Selinexor-based regimens in patients with multiple myeloma after prior anti-B-cell maturation antigen treatment

Muhamed Baljevic et al. EJHaem. .

Abstract

There is a lack of consensus on therapy sequencing in previously treated multiple myeloma, particularly after anti-B-cell maturation antigen (BCMA) therapy. Earlier reports on selinexor (X) regimens demonstrated considerable efficacy in early treatment, and after anti-BCMA-targeted chimeric antigen receptor-T cell therapy. Here, we present data from 11 heavily pretreated patients who predominantly received BCMA-antibody-drug conjugate therapy. We observe that X-containing regimens are potent and achieve durable responses with numerically higher overall response and clinical benefit rates, as well as median progression free survival compared to patients' prior anti-BCMA therapies, despite being used later in the treatment course. In an area of evolving unmet need, these data reaffirm the efficacy of X-based regimens following broader anti-BCMA therapy.

Keywords: anti‐BCMA; multiple myeloma; selinexor.

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Conflict of interest statement

Muhamed Baljevic ‐ Consultancy: BMS/Celgene, Cardinal Health; Sanofi‐Genzyme. Advisory Boards: Oncopeptides, Janssen Research, Karyopharm, BMS/Celgene, Sanofi‐Genzyme. Speaker: NCCN, CurioScience, AJH. Cristina Gasparetto ‐ Leadership: Celgene. Consulting or Advisory Role: Abbvie/Genentech; Celgene; GlaxoSmithKline; Janssen; Karyopharm Therapeutics; Sanofi. Speaker: GlaxoSmithKline; Karyopharm Therapeutics; Sanofi. Travel, Accommodations, Expenses: Celgene; Karyopharm Therapeutics. Gary J. Schiller ‐ clinical research support from KaryopharmSascha A. Tuchman ‐ Consulting: Caelum, Sanofi, Shattuck Labs, Janssen; Research support: Karyopharm, Sanofi, Caelum, Janssen. Natalie S. Callander ‐ Research Funding: Cellectar. Suzanne Lentzsch ‐ Leadership: Caelum Biosciences. Stock and Other Ownership Interests: Caelum Biosciences. Consulting or Advisory Role: Abbvie/Genentech; Amgen; Caelum Biosciences; Celularity; GlaxoSmithKline; Janssen; Sanofi; Sorrento Therapeutics; Takeda. Speaker: Clinical Care Options/NCCN; PeerView. Research Funding: Karyopharm Therapeutics; Sanofi. Patents, Royalties, Other Intellectual Property: Patent 11‐1F4 mAb for use in AL Amyloidosis. Travel, Accommodations, Expenses: Janssen. Jorge Monge ‐ Consultancy for BMS, Research funding from Karyopharm Therapeutics. Rami Kotb ‐ Research funding: Merck, Sanofi. Ownership/Share holder: Karyopharm. Honoraria: Celgene/BMS, Janssen, Takeda, Amgen, Sanofi, Merck, Pfizer. Nizar J. Bahlis ‐ Consultancy and advisory board: BMS/Celgene, Janssen, Pfizer, Amgen, Genentech, Sanofi, Karyopharm. Research funding: PfizerDarrell White‐ Amgen, Antengene, Celgene/BMS, Forus, GSK, Janssen, Karyopharm, Sanofi, Takeda: honoraria, consultancyChristine I. Chen ‐ Consulting or Advisory Role ‐ Abbvie; AstraZeneca; Bristol‐Myers Squibb; Gilead Sciences; Janssen; Novartis; Research Funding ‐ Gilead Sciences. Heather J. Sutherland ‐ Honoraria ‐ Amgen; Bristol‐Myers Squibb; Celgene; Genzyme; Janssen; Takeda. Consulting or advisory role ‐ Amgen; Bristol‐Myers Squibb; Celgene; Janssen; Sanofi; Takeda. Sumit Madan ‐ Speaker bureau: Janssen, BMS Ad hoc advisory board/consultancy: Janssen, Takeda, Oncopeptide, Pfizer. Richard LeBlanc‐ Consultancy/advisory board: BMS Canada; Janssen Inc.; Amgen Canada; Takeda Canada; Sanofi Canada. Michael Sebag ‐ Honoraria: Amgen; Bristol‐Myers Squibb; Celgene; Janssen‐Ortho; Karyopharm Therapeutics; Novartis; Takeda. Research funding: Janssen. Patents, Royalties, Other. Intellectual Property: Patent but with no associated royalties or profit. Christopher P. Venner ‐ Honoraria: Amgen; Bristol‐Myers Squibb; GlaxoSmithKline; Janssen; Sanofi; Takeda. William I. Bensinger ‐ Speakers bureau: Janssen, BMS, Amgen, Takeda, SanofiDane R. Van Domelen, Ohad S. Bentur, and Chris Zhang are employees of Karyopharm Therapeutics. Andrew DeCastro, Jatin J. Shah, and Michael G. Kauffman are former employees of Karyopharm Therapeutics. Sharon Shacham is a former employee of Karyopharm Therapeutics and holds patents (8999996, 9079865, 9714226, PCT/US12/048319, and I574957) on hydrazide‐containing nuclear transport modulators and uses and holding pending patents (PCT/US12/048319, 499/2012, PI20102724, and 2012000928) on hydrazide‐containing nuclear transport modulators and uses. Brea Lipe ‐ Consultant for BMS, Janssen, GSK.

Figures

FIGURE 1
FIGURE 1
Treatment outcomes in response to X‐containing regimens. (A) Response of multiple myeloma (MM) markers to treatments. *Ongoing therapy at data cutoff (March 01, 2022). High‐risk cytogenetics defined as presence of del(17p), t(4;14), t(14;16), 1q+, or extramedullary myeloma at screening. Patient 3 with minor response (MR) also had an unconfirmed partial response (PR). (B) Swimmer plot of selinexor dosing and response assessments over time. Each point on each line of the swimmer plot represents dosing of selinexor. CP, clinical disease progression; d, dexamethasone; E, elotuzumab; EMD, extra medullary disease; K, carfilzomib; MR, minimal response; P, pomalidomide; PD, progressive disease; PR, partial response; SD, stable disease; V, bortezomib; VGPR, very good partial response; X, selinexor
See this image and copyright information in PMC

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