Comparison of Treatment Outcomes with V-EPOCH Vs DA-EPOCH for First-Line Plasmablastic Disease

Background: Plasmablastic lymphoma (PBL) is a rare, aggressive B cell non-Hodgkin lymphoma. Plasmablastic myeloma (PBM) is a rare, aggressive form of multiple myeloma (MM), typically defined by presence of ≥2% clonal plasmablasts, and carries a similarly poor prognosis. These two entities can be challenging to distinguish clinically due to overlapping histopathologic features. There is heterogeneity in treatments and overall survival (OS) is poor, ranging from 12-18 months. Dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin (DA-EPOCH) is associated with improved OS compared to cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) despite no difference in overall response rate (ORR). Recently, the addition of bortezomib to DA-EPOCH (V-EPOCH) has further improved outcomes compared to historical controls. Here, we sought to examine differences in response and long-term outcomes between patients with PBL and PBM receiving first-line V-EPOCH vs DA-EPOCH.

Methods: We conducted a single-center, retrospective study examining adult patients diagnosed with PBL or PBM treated with either V-EPOCH or DA-EPOCH as first-line therapy between 2012 and 2022. Baseline clinical variables were collected. ORR, progression-free survival (PFS), and OS were compared between treatment groups. ORR was defined as partial response (PR) + complete response (CR) by Lugano criteria for PBL and extramedullary PBM with simultaneous presence of PR + very good partial response (VGPR) + CR by International Myeloma Working Group response criteria for PBM. PFS was defined from first-line treatment initiation to progression or death and OS was defined from first-line treatment initiation to death with censoring of those alive at last follow-up. Comparisons used Wilcoxon Rank-sum test for continuous variables and Fisher's Exact test for categorical variables. Kaplan-Meier method was used to generate survival functions with log-rank test used to compare groups.

Results: In total, 26 patients with plasmablastic disease were identified, 23 (88%) had PBL and 3 (12%) had PBM. Eighteen (69%) received V-EPOCH and 8 (31%) received DA-EPOCH. All PBM patients received V-EPOCH. Of the PBL patients, 15 (65%) received V-EPOCH and 8 (35%) received DA-EPOCH. With respect to first-line therapy received, groups were similar between V-EPOCH and DA-EPOCH in terms of age (median 55 years [range: 28, 73] vs 56 years [range: 29, 78], p=0.91), sex (22% female vs 25% female, p=1.0), Eastern Cooperative Oncology Group (ECOG) performance status (83% 0-1, 17% 2, 0% 3 vs 75% 0-1, 13% 2, 13% 3, p=0.19), stage of disease (33% stage I-II, 67% stage III-IV vs 14% stage I-II vs 86% stage III-IV, p=0.38), presence of extranodal disease (94% vs 63%, p=0.07), HIV positivity (33% vs 57%, p=0.38), EBER positivity (61% vs 86%, p=0.36), MYC rearrangements (39% vs 83%, p=0.16), Ki67>80% (69% vs 43%, p=0.36), median baseline lactate dehydrogenase level (241 units/liter [range: 122, 2949] vs 320 [range: 168, 1103], p=0.85) and median international prognostic index (IPI) score (2 [range: 1, 4] vs 2 [range: 0, 3], p=0.47). The median follow-up time was 32.9 months.

In the entire cohort, ORR for V-EPOCH was 50% (95% CI: 26, 74) and for DA-EPOCH was 50% (95% CI: 16, 84, p=1.0). Median PFS for V-EPOCH was 7.1 months (95% CI: 4.3, not reached [NR]) and for DA-EPOCH was NR (95% CI: 0.9, NR, p=0.88). At 12 months follow-up, 47% (95% CI: 23, 68) of patients receiving V-EPOCH and 50% (95% CI: 15, 77) of patients receiving DA-EPOCH were alive and progression-free. Median OS was not reached in either the V-EPOCH or DA-EPOCH groups (95% CI: 6.8, NR and 1.4, NR, respectively p=0.88). At 12 months follow-up, 77% (95% CI: 49, 91) of patients receiving V-EPOCH and 63% (95% CI: 23, 86) of patients receiving DA-EPOCH were alive. Six (33%) patients in the V-EPOCH group underwent consolidative autologous stem cell transplant while no patients in DA-EPOCH group did. Seven (39%) and 2 (25%) patients went on to receive second-line therapy in the V-EPOCH and DA-EPOCH groups, respectively.

Conclusion: Plasmablastic disease, either PBL or PBM, is a rare and challenging diagnosis. We report no statistically significant differences between V-EPOCH and DA-EPOCH with regards to ORR, PFS, or OS. Outcomes for these patients remain poor and targeted therapies are needed to improve long-term survival.

Voorhees:Recordati: Consultancy, Research Funding; Incyte/Morphosys: Research Funding; AbbVie: Membership on an entity's Board of Directors or advisory committees, Research Funding; Viracta: Research Funding; Kite: Research Funding; Novartis: Consultancy; Genmab: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. Shindiapina:Pfizer: Other: Research Funding; Bristol Myers Squibb: Other: Research funding. Baiocchi:ATARABio: Consultancy, Other: Advisory Board; Viracta Therapeutics: Consultancy, Current holder of stock options in a privately-held company, Other: Advisory Board; Prelude Therapeutics: Other: Advisory Board, Research Funding; Codiak Biosciences: Research Funding; Agenus: Other: Involved in supply of drug (vaccine) and product development. Rosko:Curio Science: Honoraria; Physicians Education Resource LLC: Honoraria; FDA: Consultancy; Clinical Care Options CMM: Honoraria; Sanofi: Research Funding.