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Bridging advanced myeloma patients to subsequent treatments and clinical trials with classical chemotherapy and stem cell support

Bone Marrow Transplantation volume 58, pages 80–86 (2023)Cite this article

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Abstract

Rapidly progressing relapsed/refractory multiple myeloma (RRMM) patients with compromised marrow have limited treatment options. Thus, non-myeloablative chemotherapy with a stem cell boost (SCB) may provide disease control and hematopoietic improvement as bridge to subsequent therapies. We identified 96 patients who received a SCB between January 2011 and December 2019 at the Mount Sinai Hospital. Patients had a median age of 64 years, received a median of 7 prior lines of therapy and 68 and 42% were triple-class and penta-drug refractory, respectively. Chemotherapy included melphalan (MEL) (n = 16), melphalan + carmustine (BCNU/MEL) (n = 52) or a variant of DCEP (dexamethasone, cyclophosphamide, etoposide, cisplatin) (n = 28). Median time to neutrophil recovery was 10 days and was significantly lower with DCEP (8 days) compared to MEL and BCNU/MEL (10–11 days) (p = 0.0047). Time to progression, progression-free survival and overall survival were 3.19, 2.7 and 8.38 months, respectively. The BCNU/MEL group had the highest response rate of 85% (p = 0.05), clinical benefit rate of 94% (p = 0.0014), progression-free survival of 3.3 months (p = 0.4) and overall survival of 8.7 months (p = 0.5). Sixty-six patients (69%) were bridged to new lines of therapy, including clinical trials. Non-myeloablative chemotherapy with SCB provides rapid disease control and marrow recovery with potential to receive further therapy.

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Fig. 1: Clinical outcomes of patients according to conditioning regimen.

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Data availability

The datasets generated during and analysed during the current study are available in the FigShare repository, [https://doi.org/10.6084/m9.figshare.21286503].

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Authors and Affiliations

  1. Division of Hematology and Medical Oncology, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA

    Tarek H. Mouhieddine, Santiago Thibaud, Benjamin Puliafito, Rita Jakubowski, Larysa Sanchez, Adriana Rossi, Cesar Rodriguez, Shambavi Richard, Hearn Jay Cho, Samir Parekh, Ajai Chari, Amir Steinberg & Joshua Richter

  2. Department of Population Health Science and Policy, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA

    Erin Moshier

  3. Department of Pharmacy, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA

    Mohammad Rattu

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Contributions

Conceptualization: THM and JR; Methodology: EM; Investigation: THM, ST, BP, MR, RJ and AS; Writing – Original Draft: THM; Writing – Review & Editing: all authors; Resources: JR; Supervision: JR.

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Correspondence to Joshua Richter.

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Competing interests

THM received advisory board fees from Legend Biotech. LS received consulting fees from Takeda. SR received honoraria from Karyopharm and Janssen, and advisory board fees from Karyopharm and Celgene/Bristol Myers Squibb, and research support from Janssen, Celgene/Bristol Myers Squibb, C4 Therapeutics. AR received advisory board fees from Celgene/Bristol Myers Squibb, Janssen, Sanofi, and GlaxoSmithKline. HJC is an employee of the Multiple Myeloma Research Foundation, and received research funding from Celgene/Bristol Myers Squibb, and Takeda. CR received consulting fees from Janssen, Artica, Takeda, Amgen, Karyopham, and Caelum Biosciences. SP received advisory board fees from GRAIL and research support from Celgene/Bristol Myers Squibb, Amgen, and Karyopharm. A.C. received consulting fees from Amgen, Celgene/Bristol Myers Squibb, Janssen, Karyopharm, and Takeda, and advisory board fees from Amgen, Celgene/Bristol Myers Squibb, Janssen, Karyopharm, Takeda, Sanofi, and Seattle Genetics, and research support from Amgen, Array Biopharma, Celgene/Bristol Myers Squibb, GlaxoSmithKline, Janssen, Takeda, Novartis, Oncoceutics, Pharmacyclics and Seattle Genetics. SJ received advisory board fees and consulting fees from Celgene/Bristol Myers Squibb, Janssen, Legend Biotech, Karyopharm, Sanofi and Takeda. J.R. received speaking fees from Celgene/Bristol Myers Squibb, Sanofi, and Janssen, and advisory board fees from Celgene/Bristol Myers Squibb, Janssen, Celgene/Bristol Myers Squibb, Karyopharm, Sanofi, X4 Pharmaceuticals, Oncopeptides, Adaptive Biotechnologies, Secura Bio, Astrazeneca, and Takeda, and consulting fees from Celgene/Bristol Myers Squibb, Secura Bio, and Oncopeptides. EM, ST, BP, MR, RJ, and AS declare no potential conflict of interest.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Informed consent was obtained from all individual participants included in the study.

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Mouhieddine, T.H., Moshier, E., Thibaud, S. et al. Bridging advanced myeloma patients to subsequent treatments and clinical trials with classical chemotherapy and stem cell support. Bone Marrow Transplant 58, 80–86 (2023). https://doi.org/10.1038/s41409-022-01848-7

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