Scientific publications
Recovery of uninvolved heavy/light chain pair immunoparesis in newly diagnosed transplant-eligible myeloma patients complements the prognostic value of minimal residual disease detection. Scientific Publication
Sunil Lakhwani 1 , Laura Rosiñol 2 , Noemí Puig 3 , Miguel-Angel Pico-Picos 4 , Laura Medina-González 4 , Joaquín Martínez-López 5 , Bruno Paiva 6 , María-Teresa Cedena 7 , Albert Oriol 8 , Rafael Ríos-Tamayo 9 , María-Jesús Blanchard 10 , Isidro Jarque 11 , Joan Bargay 12 , José-María Moraleda 13 , Estrella Carrillo-Cruz 14 , Anna Sureda 15 , Isabel Krsnik 9 , Esther González 16 , Luis Felipe Casado 17 , Josep M Martí 18 , Cristina Encinas 19 , Felipe De Arriba 20 , Luis Palomera 21 , Antonia Sampol 22 , Yolanda González-Montes 23 , Cristina Motlló 24 , Javier De La Cruz 25 , Rafael Alonso 7 , María-Victoria Mateos 3 , Joan Bladé 2 , Juan-José Lahuerta 25 , Jesús San-Miguel 6 , Miguel-Teodoro Hernández 26
Abstract
Immunoparesis (IP) in multiple myeloma (MM) patients can be measured by classic assessment of immunoglobulin (Ig) levels or by analysis of the uninvolved heavy/light chain pair of the same immunoglobulin (uHLC) by the Hevylite® assay.
In this study we evaluate the prognostic value of recovery from IP measured by classic total Ig and uHLC assessment in newly diagnosed MM transplant-eligible (NDMM-TE) patients with intensive treatment and its association with minimal residual disease (MRD).
Patients were enrolled and treated in the PETHEMA/GEM2012MENOS65 trial and continued in the PETHEMA /GEM2014MAIN trial. Total Ig (IgG, IgA and IgM) and uHLC were analyzed in a central laboratory at diagnosis, after consolidation treatment and after the first year of maintenance.
MRD was analyzed by next-generation flow cytometry after consolidation (sensitivity level 2x10-6). We found no differences in progression-free survival (PFS) between patients who recovered and patients who didn't recover from IP after consolidation when examining classic total Ig and uHLC.
However, after the first year of maintenance, in contrast to patients with classic IP, patients with recovery from uHLC IP had longer PFS than patients without recovery, with hazard ratio of 0.42 (95% confidence interval [CI]: 0.21-0.81; P=0.008). Multivariate analysis with Cox proportional-hazards regression models confirmed recovery from uHLC IP after the first year of maintenance as an independent prognostic factor for PFS, with an increase in C-statistic of 0.05 (95% CI: -0.04 to 0.14; P<0.001) when adding uHLC IP recovery.
Moreover, we observed that MRD status and uHLC IP recovery affords complementary information for risk stratification. In conclusion, recovery from uHLC IP after 1 year of maintenance is an independent prognostic factor for PFS in NDMM-TE patients who receive intensive treatment. Immune reconstitution, measured as recovery from uHLC IP, provides complementary prognostic information to MRD assessment (clinicaltrials gov. Identifiers: NCT01916252 and NCT02406144).
CITATION Haematologica. 2024 Jun 1;109(6):1909-1917. doi: 10.3324/haematol.2023.284154
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