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. 2020 May 26;4(10):2163-2171.
doi: 10.1182/bloodadvances.2020001508.

Prolonged lenalidomide maintenance therapy improves the depth of response in multiple myeloma

Rafael Alonso  1   2 , María-Teresa Cedena  1   2 , Sandy Wong  3 , Nina Shah  3 , Rafael Ríos-Tamayo  4 , José M Moraleda  5 , Javier López-Jiménez  6 , Cristina García  1   2 , Natasha Bahri  3 , Antonio Valeri  1   2 , Ricardo Sánchez  1   2 , Luis Collado-Yurrita  7 , Thomas Martin  3 , Jeffrey Wolf  3 , Juan-José Lahuerta  1   2 , Joaquín Martínez-López  1   2   3
Affiliations

Prolonged lenalidomide maintenance therapy improves the depth of response in multiple myeloma

Rafael Alonso et al. Blood Adv. .

Abstract

Lenalidomide is an immunomodulatory drug approved for maintenance treatment in newly diagnosed multiple myeloma, and it has been shown to improve progression-free survival (PFS) and, in several studies, overall survival. Nevertheless, the impact of prolonged treatment with lenalidomide on the kinetics of minimal residual disease (MRD) and its prognostic impact have not been studied in depth. To obtain better knowledge in this regard, we retrospectively analyzed 139 patients who received lenalidomide maintenance in real-world clinical practice and whose MRD levels were observed during the treatment period by multiparametric flow cytometry or next-generation sequencing with a sensitivity of at least 10-4. Lenalidomide maintenance correlated with an increased depth of the disease response, with 38.1% of patients achieving maximal response during maintenance. Moreover, 34.3% of patients who were MRD positive after induction treatment achieved MRD-negative status during maintenance and ultimately had improved PFS. Sequential MRD assessments identified patients with progressively decreasing MRD levels who also had better PFS outcomes, compared with patients not showing a decreasing pattern of MRD. These results support the role of maintenance therapy, not only to sustain, but also to increase the depth of disease response with a PFS benefit. In addition, MRD monitoring during maintenance identifies patients with better prognosis and may help in their clinical management.

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Conflict of interest statement

Conflict-of-interest disclosure: N.S. reports consultancy and honoraria from Celgene, Janssen, Bluebird Bio, Sutro Biopharma, Genentech, Seattle Genetics, Oncopeptides, Karoypharm, Surface Oncology, Precision Biosciences, GSK, Nektar, Amgen, Indapta Therapeutics, Sanofi, and Indapta Therapeutics. R.R.-T. reports consulting or advisory role for Janssen and Celgene. J.M.-L. reports grants from Celgene, Janssen, and BMS, received during the current study, but not applied to the work; consultancy and honoraria from Incyte, Roche, Novartis, and BMS; and holds a patent (Método de cuantificación de Enfermedad Mínima Residual en un sujeto) for quantifying the level of MRD in a subject and is receiving royalties. The remaining authors declare no competing financial interests.

Figures

None
Graphical abstract
Figure 1.
Figure 1.
Comparison of response status at the beginning of lenalidomide maintenance and at maximal response. PR, partial response; VGPR, very good partial response.
Figure 2.
Figure 2.
PFS according to MRD status. (A) At maximal response during or after maintenance treatment with lenalidomide. (B) At the beginning of maintenance treatment with lenalidomide.
See this image and copyright information in PMC

References

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