Efficiency of lenalidomide, bortezomib and prednisone (RVP) in patients with newly diagnosed multiple myeloma

Objective: to study the efficacy and safety of the antitumor RVP program (lenalidomide, bortezomib, prednisone) as a first-line therapy in patients with multiple myeloma (MM).
Materials and methods. A prospective study involved 39 patients with MM (15 women, 24 men), median age 61 years (30–76 years). All patients had Durie–Salmon stage III disease. According to the paraprotein isotype variant, 19 patients (48.7 %) had Gk myeloma, 8 (20.5 %) had Gλ, 4 (10.2 %) – Ak, 1 – Aλ, 1 – Dk, 1 – paraproteinemia Bens-Jones k and 1 – Bens-Jones λ, 2 – Dλ, and 2 patients – nonsecreting MM. The average level of plasma cells in the bone marrow was 31.7 % (0.8–80.0 %). In 14 (35.8 %) patients there were plasmacytomas of various localization (spine, cranial bones, clavicle, pleura). Nine (23.0 %) patients had renal failure, requiring the start of renal replacement therapy. The average Karnovsky index in the study group was 50 %. All patients received RVP therapy (lenalidomide 25 mg in 1–14 days, bortezomib 1.3 mg subcutaneously in 1, 4, 8, 11 days, prednisolone 60 mg/m2; the interval between courses was 42 days) as the first line therapy. Evaluation of therapy efficacy, characterized by overall survival, objective response rates (the number of complete, very good partial and partial remissions) was performed after 6 treatment courses.
Results. The median follow-up was 15 months; the median of overall survival was not achieved. Objective antitumor response achieved in 29 (74.3 %) patients, including complete remissions in 3 (7.6 %), very good partial remissions – in 7 (17.9 %), partial remissions – in 19 (48.7 %) patients. In 2 out of 9 patients who received renal replacement therapy, independence from dialysis therapy was achieved. Cases of III–IV stage hematological and non-hematological toxicity in the study were not noted.
Conclusion. The antitumor RVP program showed high efficacy and safety as a first-line therapy in a non-selective group of patients, including those with a complicated MM course.

1. Katodritou E., Terpos E., Delimpasi S. et al. Real-world data on prognosis and outcome of primary plasma cell leukemia in the era of novel agents: a multicenter national study by the Greek Myeloma Study Group. Blood Cancer J 2018;8(3):31. DOI: 10.1038/s41408-018-0059-6. PMID: 29523783.

2. Менделеева Л.П. Как мы лечим множественную миелому в реальной клинической практике. Ежегодный гематологический форум Центрального Федерального округа. Тула, 26 мая 2018 г. [Mendeleeva L.P. How do we treat multiple myeloma in real clinical practice? Annual Hematological Forum of the Central Federal District. Tula, May 26, 2018. (In Russ.)].

3. Durie B.G., Hoering A., Abidi M.H. et al. Bortezomib with lenalidomide and dexamethasone versus lenalidomide and dexamethasone alone in patients with newly diagnosed myeloma without intent for immediate autologous stem-cell transplant(SWOG S0777): a randomised, open-label, phase 3 trial. Lancet 2017;389(10068):519–27. DOI: 10.1016/S0140-6736(16)31594-X. PMID: 28017406.

4. Митина Т.А., Голенков А.К., Трифонова Е.В. и др. Эффективность бортезомиба, мелфалана, преднизолона (ВМП) у пациентов с впервые выявленной множественной миеломой. Medline.ru 2013;14(4):1030–50. [Mitina T.A., Golenkov A.K., Trifonova E.V. et al. Efficacy of bortezomib, melpahlan and prednisolone (VMP) in patients with newly diagnosed multiple myeloma. Medline.ru 2013;14(4):1030–50. (In Russ.)].

5. Spicka I., Mateos M.V., Redman K. et al. An overview of the VISTA trial: newly diagnosed, untreated patients with multiple myeloma ineligible for stem cell transplantation. Immunotherapy 2011;3(9):1033–40. DOI: 10.2217/imt.11.104. PMID: 21913826.

6. Moreau P., Touzeau C. Global approaches in myeloma: critical trials that may change practice. Am Soc Clin Oncol Educ Book 2018;23(38):656–61. DOI: 10.1200/EDBK_200841. PMID: 30231332.

7. Chauhan D., Singh A.V., Ciccarelli B. et al. Combination of novel proteasome inhibitor NPI-0052 and lenalidomide trigger in vitro and in vivo synergistic cytotoxicity in multiple myeloma. Blood 2010;115(4):834–45. DOI: 10.1182/blood-2009-03-213009. PMID: 19965674.

8. Gandhi A.K., Kang J., Capone L. et al. Dexamethasone synergizes with lenalidomide to inhibit multiple myeloma tumor growth, but reduces lenalidomideinduced immunomodulation of T and NK cell function. Curr Cancer Drug Targets 2010;10(2):155–67. DOI: 10.2174/156800910791054239. PMID: 20088798.

9. Митина Т.А., Голенков А.К., Трифонова Е.В. и др. Эффективность леналидомида, бортезомиба и преднизолона при лечении пациентов с рецидивирующей и рефрактерной множественной миеломой. Онкогематология 2015;10(4):8–14. DOI: 10.17650/1818-8346-2015-10-4-8-14. [Mitina T.A., Golenkov A.K., Trifonova E.V. et al. Efficacy of lenalidomide, bortezomib, and prednisolone in patients with relapsed or refractory multiple myeloma. Onkogematologiya = Oncohematology 2015;10(4):8–14. (In Russ.)].

10. Kumar S., Paiva B., Anderson K.C. et al. International Myeloma Working Group consensus criteria for response and minimal residual disease assessment in multiple myeloma. Lancet Oncol 2016;17(8):e328–46. DOI: 10.1016/S1470-2045(16)30206-6. PMID: 27511158.

11. Митин А.Н., Литвина М.М., Донецкова А.Д. и др. Динамика восстановления Т-лимфоцитов после индукционного курса химиотерапии у пациентов с впервые выявленной множественной миеломой. Иммунология 2014;35(4):209–14. [Mitin A.N., Litvina M.M., Donetskova A.D. et al. Dynamics of T-lymphocytes recovery after induction chemotherapy in patients with newly diagnosed multiple myeloma. Immunologiya = Immunology 2014;35(4):209–14. (In Russ.)].