Original article

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Anti-CD38 monoclonal antibody impairs CD34+ mobilization and affects clonogenic potential in multiple myeloma patients

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Key words: multiple myeloma, anti-CD38 monoclonal antibody, mobilization, collection, apheresis

Abstract

Background - Induction with daratumumab-based regimens followed by autologous stem cell transplantation is the current standard for newly diagnosed multiple myeloma (NDMM) patients eligible for intensive chemotherapy. However, concerns emerged regarding potential negative effects following daratumumab-based treatment on CD34+ mobilization. We here compared CD34+ mobilization and clonogenic potential between daratumumab and non-daratumumab based therapy without upfront plerixafor administration among patients affected by NDMM.

Materials and methods - Clinical, mobilization and clonogenic data from 41 consecutively enrolled NDMM patients were analyzed. Patients underwent collection of autologous CD34+ by apheresis at the ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy, from January 2021 to March 2023. Clonogenicity analysis was performed on BFU-E and CFU-GM.

Results - Seventy-five percent of daratumumab-treated patients underwent >1 apheresis, compared to 24% of non-daratumumab patients (p=0.0017). Daratumumab-treated patients had significantly lower CD34+ count (mean 38 vs 79/μL, respectively; p=0.0011), with a median CD34+ harvest of  3.98×106/kg (range 1.68-9.18) vs 6.87×106/kg (range 1.63-16.85) in non-daratumumab-treated (p=0.0006). In multivariate analysis the likelihood of undergoing >1 apheresis was significantly higher in older patients (OR 1.2, 95% CI 1-1.4, Z=2.10, p=0.03) and daratumumab-treated patients (OR 15, 95% CI 2.8-129, p=0.004). Moreover, daratumumab-based induction therapy demonstrated an independent negative association with BFU-E colony formation (p=0.0148), even when accounting for patient age and CD34+ levels.

Discussion - Our findings underscore the impact of daratumumab-based treatment on CD34+ mobilization in a real-life, upfront plerixafor-free population of NDMM patients. Higher probability of requiring multiple apheresis occurred among daratumumab-treated patients. Interestingly, the observation that daratumumab might negatively impact BFU-E colony formation, independent of CD34+ cell count, offers novel biological perspectives. Appropriate strategies should be adopted by the Apheresis teams to mitigate these potential negative effects.

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Authors

Arianna Zappaterra - Department of Medicine and Surgery, Milano-Bicocca University, Monza, Italy; Hematology Division, Fondazione IRCCS San Gerardo dei Tintori Hospital, Monza, Italy; Hematology Division, ASST Grande Ospedale Metropolitano Niguarda, Milano, Italy

Ivan Civettini - Department of Medicine and Surgery, Milano-Bicocca University, Monza, Italy; Hematology Division, Fondazione IRCCS San Gerardo dei Tintori Hospital, Monza, Italy https://orcid.org/0000-0002-7707-584X

Anna Maria Cafro - Hematology Division, ASST Grande Ospedale Metropolitano Niguarda, Milano, Italy

Laura Pezzetti - Cellular Therapy Laboratory, ASST Grande Ospedale Metropolitano Niguarda, Milano, Italy

Silvia Pierini - Department of Medicine and Surgery, Milano-Bicocca University, Monza, Italy; Hematology Division, Fondazione IRCCS San Gerardo dei Tintori Hospital, Monza, Italy

Michela Anghilieri - Onco-hematology Division, Manzoni Hospital, Lecco, Italy

Laura Bellio - Immunohematology and Transfusion Medicine Service, ASST Grande Ospedale Metropolitano Niguarda, Milano, Italy

Paola Bertazzoni - Hematology Division, ASST Grande Ospedale Metropolitano Niguarda, Milano, Italy

Giovanni Grillo - Hematology Division, ASST Grande Ospedale Metropolitano Niguarda, Milano, Italy

Periana Minga - Hematology Division, ASST Grande Ospedale Metropolitano Niguarda, Milano, Italy

Maria Luisa Pioltelli - Hematology Division, ASST Grande Ospedale Metropolitano Niguarda, Milano, Italy

Emanuele Ravano - Hematology Division, ASST Grande Ospedale Metropolitano Niguarda, Milano, Italy

Marianna Sassone - Onco-hematology Division, Manzoni Hospital, Lecco, Italy

Clara Virginia Viganò - Onco-hematology Division, Manzoni Hospital, Lecco, Italy

Elisabetta Bice Volpato - Immunohematology and Transfusion Medicine Service, ASST Grande Ospedale Metropolitano Niguarda, Milano, Italy

Carlo Gambacorti-Passerini - Department of Medicine and Surgery, Milano-Bicocca University, Monza, Italy; Hematology Division, Fondazione IRCCS San Gerardo dei Tintori Hospital, Monza, Italy

Silvano Rossini - Immunohematology and Transfusion Medicine Service, ASST Grande Ospedale Metropolitano Niguarda, Milano, Italy

Roberto Cairoli - Department of Medicine and Surgery, Milano-Bicocca University, Monza, Italy; Hematology Division, ASST Grande Ospedale Metropolitano Niguarda, Milano, Italy

Roberto Crocchiolo - Servizio di Immunoematologia e Medicina Trasfusionale, ASST Grande Ospedale Metropolitano Niguarda, Milano https://orcid.org/0000-0001-8473-202X

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