Beneficial Effect of Lenalidomide-Dexamethason Treatment in Relapsed/Refractory Multiple Myeloma Patients: Results of Real-Life Data From 11 Hungarian Centers

Abstract

In Hungary, the cost of lenalidomide-based therapy is covered only for relapsed multiple myeloma (MM) patients, therefore lenalidomide is typically used in the second-line either as part of a triplet with proteasome inhibitors or as a doublet. Lenalidomide-dexamethasone is a standard treatment approach for relapsed/refractory MM, and according to recent large randomized clinical trials (RCT, the standard arm of POLLUX, ASPIRE, TOURMALINE), the progression-free survival (PFS) is expected to be approximately 18 months. We surveyed ten Hungarian centers treating MM and collected data of 278 patients treated predominantly after 2016. The median age was 65 years, and patients were distributed roughly equally over the 3 international staging system groups, but patients with high risk cytogenetics were underrepresented. 15.8% of the patients reached complete response, 21.6% very good partial response, 40.6% partial response, 10.8% stable disease, and 2.5% progressed on treatment. The median PFS was unexpectedly long, 24 months, however only 9 months in those with high risk cytogenetics. We found interesting differences between centers regarding corticosteroid type (prednisolone, methylprednisolone or dexamethasone) and dosing, and also regarding the choice of anticoagulation, but the outcome of the various centers were not different. Although the higher equivalent steroid dose resulted in more complete responses, the median PFS of those having lower corticosteroid dose and methylprednisolone were not inferior compared to the ones with higher dose dexamethasone. On multivariate analysis high risk cytogenetics and the number of prior lines remained significant independent prognostic factors regarding PFS (p < 0.001 and p = 0.005). Our results show that in well-selected patients Lenalidomide-dexamethasone can be a very effective treatment with real-world results that may even outperform those reported in the recent RCTs. This real world information may be more valuable than outdated RCT data when treatment options are discussed with patients.

Keywords: lenalidomide; myeloma; real life; relapsed; treatment.

FIGURE 1

Survival of patients. Overall and progression-free survival of the whole cohort (A); Progression-free survival according to Age (B), number of prior lines (C), renal function (D), FISH (E), and ISS (F). Both PFS and OS have exceeded what was expacted based on the pivotal randomized clinical trials [2]. Patients with renal failure and high risk cytogenetics were benefited less from Rd treatment. Abrreviations: FISH, fluorescence in situ hybridization; GFR, glomerular filtration rate; ISS, international staging system; OS, overall survival; PFS, progression free survival; Rd, lenalidomide-dexamethason.

FIGURE 2

Progression-free survival according to response (A), whether a third drug was added (B), lenalidomide dose (C), cordicosteroid type (D) and dose (E), and thromboprophylaxis type (F). Patients with deeper responses had longer PFS. In some cases with suboptimal response, a third drug (usually bortezomib) was added to Rd, but the outcome of these patients remained inferior compared to others. Importantly, the corticosteroid type (dexamethasone or methylprednisolone-a frequently used replacement of dexamethasone in Hungary) and dose did not have an effect on PFS. Abrreviations: CR, complete response; LMWH, low-molecular-weight heparin; NOAC, novel oral anticoagulants; PD, progressive disease; PFS, progression free survival; PR, partial response; Rd, lenalidomide-dexamethason; SD, stable disease; VGPR, very good partial response; VKA, vitamin K antagonists. *dexamethasone (5 mg methylprednisolone is equivalent with 1 mg dexamethasone).