Single-Center Experience of Carfilzomib-Based Combinations for Patients with Lymphoplasmacytic Lymphoma

Abstract

Single-Center Experience of Carfilzomib-based Combinations for patients with Lymphoplasmacytic Lymphomas Background Use of bortezomib in Waldenstrom macroglobulinemia (WM) produces a response rate of 60-70% in treatment naïve or relapsed WM(Dimopoulos et al., 2005)(Chen et al., 2006). However, it is associated with an increased risk of peripheral neuropathy (PN). This is important considering that WM can be associated frequently with PN. Carfilzomib(K) is a second-generation proteasome inhibitor that is associated with a lower PN risk and offers a PN-sparing approach for treatment for patients(pts) with WM. In the CARD trial, K-based combinations produced a high ORR with a tolerable safety profile(Treon et al., 2014). We report our single-center experience with the use of K-based combinations in pts with treatment naïve or relapsed lymphoplasmacytic lymphoma (LPL). Patients and Methods We conducted a single-center retrospective study on an IRB-approved protocol for all pts who were treated with K-based combinations at Hackensack University Medical Center between June 2015 and July 2022. Demographic characteristics, molecular studies, treatment and response information were recorded and included in the study. Efficacy outcomes included overall response rates (ORR), progression free survival (PFS), overall survival (OS). Survival analysis was performed using the Kaplan-Meier method including PFS and Overall survival (OS). PFS was defined as time from initiation of treatment to progression of disease or death whichever occurred first. OS was defined as time from initiation of treatment to death. The consensus criteria from the 6 th International Workshop on WM were utilized for response assessment. Results We identified 36 patients with a diagnosis of WM and 1 patient with IgA-kappa LPL who were treated with K-based combinations between June 2015 and July 2022. 4 patients (10.8%) had a concomitant diagnosis of systemic light chain amyloidosis (AL). 67.6% pts were male, the median age at treatment initiation was 67.5 yrs. Majority of the pts were treatment naïve (86.4%, N=32). Data for MYD88 mutation was available in 30 pts, 93.3% (n=28) were found to have MYD88 mutation on next generation sequencing (NGS) performed on bone marrow aspirate samples. As per the RPISSWM risk stratification, 30% (9) pts were found to have poor risk, 33.3% (10) had intermediate risk and 36.7% (11) had good risk. Median bone marrow involvement by WM was 30%. The majority of the pts (91.9%, n=34) received KCD-R (Carfilzomib, cyclophosphamide, dexamethasone and rituximab) as their treatment regimen, while the remaining patients received KD-R(carfilzomib, dexamethasone and rituximab). Pts received a median of 6 cycles of treatment. ORR was found to be 97.3% (n=36) with 48.6%(n=18) pts achieving a very good partial response or better (>=VGPR). Median PFS was found to be 51.08 months and median OS was not reached (NR). Two patients needed treatment discontinuation following 1 cycle or less, due to toxicity (dyspnea, one of which was non-cardiogenic) associated with carfilzomib and were changed to an alternative regimen (Bortezomib, cyclophosphamide, dexamethasone and rituximab). Further data for toxicities are being gathered and will be presented at the meeting. Baseline characteristics and outcomes data are summarized in Table 1. Conclusions K-based combinations produce a high ORR with durable responses in patients with symptomatic LPL. Treatment discontinuation rate due to toxicity was low with only two patients needing change of therapy in our cohort. Our data supports the use of K-based combinations in pts with treatment naïve or relapsed LPL.