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Contribution of post-transplantation therapy to sustained MRD negativity in multiple myeloma: a retrospective analysis

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Abstract

Post-transplantation therapy is commonly performed in patients with myeloma and can prolong progression-free survival (PFS). However, whether post-transplantation therapy contributes to achieving and continuing MRD-negativity remains controversial. This retrospective analysis aimed to evaluate the clinical impact of post-transplantation therapy, including tandem autologous stem cell transplantation (ASCT), in myeloma patients. The subjects were 79 patients (median age: 62 years) who received induction therapy, including bortezomib and/or lenalidomide, of whom 58 underwent post-transplantation therapy. At the median follow-up time of 50 months, the 4-year PFS rate was significantly higher in patients who underwent post-transplantation therapy than those who did not (60.6% vs. 28.6%, P = 0.012). Multivariate analysis revealed post-transplantation therapy to be a significant prognostic factor for long PFS. Tandem ASCT followed by consolidation and/or maintenance therapies improved PFS and OS. The minimal residual disease (MRD)-negative rate was significantly higher in patients who underwent post-transplantation therapy than those who did not (50.9% vs. 16.7%, P = 0.006). Post-transplantation therapy contributed to sustained MRD-negativity, which predicted long PFS and overall survival. Patients frequently discontinued post-transplantation therapy due to adverse events within 4 months. In conclusion, post-transplantation therapy improved PFS and contributed to sustained MRD-negativity in myeloma patients.

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Acknowledgements

We would like to thank the attending doctors and nurses at the Jikei University Hospital and the Jikei University Kashiwa Hospital. We would also like to extend gratitude to the myeloma patients and their families for consenting to participate in our study.

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Authors and Affiliations

  1. Division of Clinical Oncology/Hematology, Department of Internal Medicine, The Jikei University School of Medicine, 3-25-8 Nishi-Shimbashi, Minato-ku, Tokyo, 105-0003, Japan

    Kazuhito Suzuki, Tadahiro Gunji, Masaharu Kawashima, Hideki Uryu, Riku Nagao, Mamiko Momoki, Hiroki Yokoyama, Hiroto Ishii, Susumu Tanoue, Takeshi Saito, Kaichi Nishiwaki & Shingo Yano

  2. Division of Clinical Oncology/Hematology, Department of Internal Medicine, The Jikei University Kashiwa Hospital, Kashiwa, Japan

    Riku Nagao, Mamiko Momoki, Hiroto Ishii & Kaichi Nishiwaki

  3. Division of Clinical Oncology/Hematology, Department of Internal Medicine, The Jikei University Daisan Hospital, Komoe, Japan

    Tadahiro Gunji & Hideki Uryu

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  1. Kazuhito Suzuki
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Correspondence to Kazuhito Suzuki.

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Conflict of interest

K. Suzuki received personal fees from Takeda Pharmaceutical Company, Janssen Pharmaceutical K.K., Sanofi, Bristol Myers Squibb, Ono Pharmaceutical Co., Ltd., outside the submitted work; H. Uryu received personal fees from Janssen Pharmaceutical K.K., Ono Pharmaceutical Co., Ltd., outside the submitted work; K. Nishiwaki reports personal fees from Pfizer and Alexion Pharmaceuticals Inc. and grants from Kyowa Kirin Co, Ltd, outside the submitted work; Dr. Yano reports grants from Kyowa Kirin, grants from Lilly Phrama, and grants from Otsuka Pharmaceutical, outside the submitted work;.the other authors declare that they have no conflict of interest.

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12185_2023_3682_MOESM1_ESM.jpeg

Supplementary file1 Fig. S1. Tandem ASCT followed by consolidation and/or maintenance therapy improved progression free survival and overall survival. a The 4year-PFS rate in the tandem ASCT plus CONS/MT group was significantly longer than those in the non-tandem ASCT plus CONS/MT group (73.7% vs 34.0%, HR 0.567, 95% CI 0.391–0.824, P = 0.002) (JPEG 125 KB). b the 4year-OS rate in the tandem ASCT plus CONS/MT group tended to be longer that those in the non-tandem ASCT plus CONS/MT group (97.0% vs 73.7%, HR 0.559, 95% CI 0.299–1.048, P = 0.056). PFS progression free survival, OS overall survival, ASCT autologous stem cell transplantation, CONS/MT consolidation and/or maintenance therapy

12185_2023_3682_MOESM2_ESM.jpeg

Supplementary file2 Fig. S2. Tandem ASCT followed by consolidation and/or maintenance therapy improved progression free survival and overall survival in the patients who achieved CR after the second ASCT. a The 4year-PFS rate in the patients who achieved CR after the second ASCT and received tandem ASCT plus CONS/MT was significantly higher than those in another group (76.7% vs 40.0%, HR 0.510, 95% CI 0.303–0.858, P = 0006). b The 4year-OS rate in the patients who achieved CR after the second ASCT and received tandem ASCT plus CONS/MT was significantly higher than those in another group (100% vs 77.0%, HR not evaluated, P = 0.019). PFS progression free survival, OS overall survival, ASCT autologous stem cell transplantation, CONS/MT consolidation and/or maintenance therapy (JPEG 113 KB)

12185_2023_3682_MOESM3_ESM.jpeg

Supplementary file3 Fig. S3. The cumulative incidence of discontinuation due to adverse events. The 4month, 1, 2 and 4years-cumulative incidence rates of discontinuation of post-transplantation therapy due to adverse events were 13.3%, 15.7%, 28.9% and 33.3%, respectively (JPEG 62 KB)

Supplementary file4 Table 1 Patient characteristics after matched-pair analysis using VRd as induction (DOCX 15 KB)

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Suzuki, K., Gunji, T., Kawashima, M. et al. Contribution of post-transplantation therapy to sustained MRD negativity in multiple myeloma: a retrospective analysis. Int J Hematol 119, 39–49 (2024). https://doi.org/10.1007/s12185-023-03682-z

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