Sustained Recovery of Uninvolved Heavy/Light Chain Pair Immunoparesis during Maintenance Discriminates Patients with Sustained Negative Minimal Residual Disease

Introduction. Immunoparesis (IP) or the suppression of uninvolved immunoglobulins (Ig) is a very common finding in multiple myeloma (MM) patients at diagnosis that confers worse prognosis. In addition to classic total Ig, IP can be measured by the uninvolved heavy/light chain pair of the same immuno...

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Published in:Blood 2023-11, Vol.142 (Supplement 1), p.1958-1958
Main Authors: Lakhwani, Sunil, Rosiñol, Laura, Puig, Noemi, Pico Picos, Miguel Angel, Medina-González, Laura, Martinez Lopez, Joaquin, Paiva, Bruno, Cedena Romero, Maria Teresa, Oriol, Albert, Ríos, Rafael, Blanchard, María Jesús, Jarque, Isidro, Bargay, Joan, Moraleda, Jose Maria, Carrillo-Cruz, Estrella, Sureda Balari, Anna Maria, Krsnik, Isabel, Gonzalez Garcia, Esther, Casado Montero, Luis Felipe, Marti Tutusaus, Josep Maria, Encinas Rodriguez, Cristina, De Arriba, Felipe, Palomera, Luis, Sampol Mayol, Antonia, González-Montes, Yolanda, Motlló, Cristina, De la Cruz, Javier, Alonso Fernández, Rafael, Mateos, Maria-Victoria, Blade Creixenti, Joan, Lahuerta Palacios, Juan Jose, San Miguel, Jesus, Hernández Garcia, Miguel Teodoro
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Language:English
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Summary:Introduction. Immunoparesis (IP) or the suppression of uninvolved immunoglobulins (Ig) is a very common finding in multiple myeloma (MM) patients at diagnosis that confers worse prognosis. In addition to classic total Ig, IP can be measured by the uninvolved heavy/light chain pair of the same immunoglobulin (uHLC). Previously, we have reported that recovery of uHLC IP in a single time point (at first year of maintenance) is an independent prognostic factor in newly diagnosed MM transplant eligible (NDMM-TE) patients with intensive treatment within a clinical trial, without significant prognostic value for recovery from classic IP in that setting. Moreover, recovery of uHLC IP affords complementary information to single time point minimal residual disease (MRD) for risk stratification. Although, negative sustained MRD is the most important evolutive favorable prognostic factor in MM, some patients relapse despite achieving negative sustained MRD. Aim. To evaluate the prognostic value of sustained uHLC IP recovery during maintenance treatment, measured by progression free survival (PFS), within a clinical trial of NDMM TE patients with intensive treatment and its potential association with sustained MRD. Patients & Methods. Patients with newly diagnosed MM enrolled in the PETHEMA/GEM2012MENOS65 trial received six cycle VRD-GEM induction, autologous hematopoietic stem cell transplantation conditioned by melphalan or busulfan plus melphalan and consolidation with two more cycles of VRD-GEM. Afterwards, patients were enrolled in the PETHEMA/GEM2014MAIN clinical trial that randomly assigned them to maintenance with lenalidomide and low-dose dexamethasone (Rd) or Rd plus ixazomib for two years. After two years, patients who achieved negative MRD stopped the treatment and patients who did not achieve MRD negativity received three more years of Rd. We analyzed uHLC in a central laboratory at diagnosis and at the first and second year of maintenance. We consider IP at diagnosis when uHLC were under lower limit of normality (LLN) and recover IP when suppressed uHLC at diagnosis reach at least LLN plus 10%. Sustained uHLC IP recovery was defined as IP recovery in the first year of maintenance that persists in the second year of maintenance. MRD was analyzed by next generation flow cytometry (sensitivity level 2x10 -6) after consolidation and at the first and second year of maintenance. Sustained MRD was defined as a negative MRD for at least 12 months that remains neg
ISSN:0006-4971
1528-0020
DOI:10.1182/blood-2023-179452