Minimal Residual Disease Status in Multiple Myeloma 1 Year After Autologous Hematopoietic Cell Transplantation and Lenalidomide Maintenance Are Associated With Long-Term Overall Survival

Author(s): Marcelo C. Pasquini, MD, MS¹; Paul K. Wallace, PhD²; Brent Logan, PhD¹; Manmeet Kaur, MPH¹; Joseph D. Tario, Jr, PhD²; Alan Howard, PhD³; Yali Zhang, MPH²; Claudio Brunstein, MD, PhD⁴; Yvonne Efebera, MD^5,6; Nancy Geller, PhD⁷; Sergio Giralt, MD⁸; Parameswaran Hari, MD, MRCP¹; Mary M. Horowitz, MD, MS¹; John Koreth, MBBS, DPhil⁹; Amrita Krishnan, MD¹⁰; Heather Landau, MD⁸; George Somlo, MD, FACP¹⁰; Nina Shah, MD¹¹; Edward Stadtmauer, MD¹²; Dan T. Vogl, MD, MSCE¹²; David H. Vesole, MD¹³; Philip L. McCarthy, MD²; Theresa Hahn, PhD²

Source: https://doi.org/10.1200/JCO.23.00934

Dr. Maen Hussein's Thoughts

MRD at year 1 can be prognostic in pt who had AutoBMT followed by maintenance linolidomide.

Please use MRD wisely … it can be expensive.

PURPOSE

Prognostic Immunophenotyping in Myeloma Response (PRIMeR) is an ancillary study of minimal residual disease (MRD) assessment for multiple myeloma by next-generation multiparameter flow cytometry (MFC). Patients were enrolled on a three-arm randomized control trial (Blood and Marrow Transplants Clinical Trials Network 0702 Stem Cell Transplant for Myeloma in Combination of Novel Agents [STaMINA]; ClinicalTrials.gov identifier: NCT01109004).

METHODS

Four hundred and thirty-five patients consented to the MRD panel, which included 10 monoclonal antibodies measured via six-color MFC. MRD was measured at baseline/preautologous hematopoietic cell transplant (BL/preAutoHCT), premaintenance (PM), and 1 year (Y1) after AutoHCT with a sensitivity of 10–5 to 10–6. The primary objective was to assess MRD-negative (MRDneg) at 1 year after AutoHCT and progression-free survival and overall survival (PFS/OS).

RESULTS

Similar to the STaMINA results, at a median follow-up of 70 months, there was no significant difference in PFS/OS by treatment arm in the PRIMeR patients. MRDneg at all three time points was associated with significantly improved PFS, and MRDneg at Y1 had significantly longer OS. Multivariate analysis of PFS, adjusting for disease risk and treatment arm, demonstrated hazard ratios (HRs) in MRD-positive patients compared with MRDneg patients at BL, PM, and Y1 of 1.55 (P = .0074), 1.83 (P = .0007), and 3.61 (P < .0001), respectively. Corresponding HRs for OS were 1.19 (P = .48), 0.88 (P = .68), and 3.36 (P < .001). Patients with sustained MRDneg or who converted to MRDneg by Y1 had similar PFS/OS.

CONCLUSION

To our knowledge, this first, prospective US cooperative group, multicenter study demonstrates that MRDneg at Y1 after AutoHCT with lenalidomide maintenance is prognostic for improved 6-year PFS and OS. Serial MRD measurements may direct trials to test how further therapy may improve long-term PFS and OS.

Author Affiliations

¹Medical College of Wisconsin, Milwaukee, WI; ²Roswell Park Comprehensive Cancer Center, Buffalo, NY; ³National Marrow Donor Program, Minneapolis, MN; ⁴University of Minnesota, Minneapolis, MN; ⁵OhioHealth, Columbus, OH; ⁶Ohio State University, Columbus, OH; ⁷National Heart, Lung and Blood Institute, Bethesda, MD; ⁸Memorial Sloan Kettering Cancer Center, New York, NY; ⁹Dana Farber Cancer Institute, Boston, MS; ¹⁰City of Hope, Duarte, CA; ¹¹University California San Francisco, San Francisco, CA; ¹²University of Pennsylvania, Philadelphia, PA; ¹³John Theurer Cancer Center, Hackensack, NJ

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