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High-dose melphalan-autologous hematopoietic cell transplantation in systemic AL amyloidosis following daratumumab-based frontline therapy

Bone Marrow Transplantation (2024)Cite this article

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The role of high-dose melphalan-autologous hematopoietic cell transplantation (HDM-AHCT) in systemic immunoglobulin light chain (AL) amyloidosis has undergone renewed scrutiny in recent years, particularly with the arrival of anti-CD38 monoclonal antibody-based frontline therapies. The ANDROMEDA trial showed that Dara-VCD (Daratumumab-Bortezomib-Cyclophosphamide-Dexamethasone) achieved a hematologic complete response (Heme-CR) rate of greater than 50% –as compared to heme-CR rates of 30–40% reported with HDM-AHCT [1, 2]. Besides infection risk, daratumumab-based (Dara-based) frontline therapy is well-tolerated and can be employed in a wide range of patients, including those with advanced cardiac dysfunction [3]. Since we can now achieve deep hematologic responses with Dara-VCD, a key unanswered question in the field is whether consolidative HDM-AHCT is still needed. In addition, for the subgroup of patients with suboptimal hematologic response to Dara-VCD, the safety and efficacy of HDM-AHCT has yet to be determined. As the role of HDM-AHCT is revisited in the context of Dara-based regimens, it remains to be seen how Dara-based frontline therapies might influence transplantation-related mortality (TRM; death within 100 days of stem cell infusion). In the initial 28-patient safety-run of the ANDROMEDA trial, 3 of 28 (11%) patients who underwent consolidative HDM-AHCT after Dara-VCD experienced TRM due to recurrent infections or septic shock [4]. Given the potential for increased morality risk with Dara-based frontline therapy followed by HDM-AHCT, we performed a retrospective cohort study to describe transplant characteristics and outcomes for patients with AL amyloidosis who underwent HDM-AHCT in the context of Dara-based induction therapy.

We extracted data for all consecutive patients with AL amyloidosis who underwent HDM-AHCT following Dara-based frontline therapy and were seen at Columbia University Irving Medical Center (CUIMC), with the data cut-off for follow-up set at 11/30/2023. Initial demographic, disease pathology (e.g., Mayo Stage, organ involvement), and laboratory values were extracted at confirmed diagnosis of light chain amyloidosis. Induction therapy regimen and response rate as well as pre-transplant characteristics were further collected. Finally, we recorded mobilization and transplantation data (e.g., number CD34+ collected) in addition to HDM-ACHT clinical outcomes. All statistical analyses were performed in JMP Pro 15.0. The study was approved by the institutional review board at CUIMC.

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Authors and Affiliations

  1. Department of Medicine, Columbia University Irving Medical Center, New York, NY, USA

    George S. Mellgard

  2. Columbia University Herbert Irving Comprehensive Cancer Center, New York, NY, USA

    Divaya Bhutani, Markus Y. Mapara, Suzanne Lentzsch & Rajshekhar Chakraborty

  3. Division of Cardiology, Columbia University Irving Medical Center, New York, NY, USA

    Mathew S. Maurer

  4. Division of Nephrology, Columbia University Irving Medical Center, New York, NY, USA

    Jai Radhakrishnan

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  1. George S. Mellgard
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Contributions

GSM, MYM, and RC conceived the study design. GSM collected patient data from electronic medical records. DB, MYM, MSM, JR, SL, and RC performed patient care. GSM wrote the first draft of the manuscript. DB, MYM, MSM, JR, SL, and RC critically reviewed the first draft and approved the final draft of the manuscript.

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Correspondence to Rajshekhar Chakraborty.

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Mellgard, G.S., Bhutani, D., Mapara, M.Y. et al. High-dose melphalan-autologous hematopoietic cell transplantation in systemic AL amyloidosis following daratumumab-based frontline therapy. Bone Marrow Transplant (2024). https://doi.org/10.1038/s41409-024-02301-7

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