Preliminary results of a phase II randomized study (ROMULUS) of polatuzumab vedotin (PoV) or pinatuzumab vedotin (PiV) plus rituximab (RTX) in patients (Pts) with relapsed/refractory (R/R) non-Hodgkin lymphoma (NHL).

8519 Background: PoV and PiV, antibody drug conjugates (ADC) containing the anti-mitotic MMAE targeting CD79b (PoV) and CD22 (PiV), showed clinical activity in Phase I. The current study aims to compare PoV and PiV + RTX in R/R DLBCL and R/R follicular lymphoma (FL). Methods: Pts were randomized to receive PoV or PiV + RTX (ADC 2.4 mg/kg + RTX 375 mg/m2) every 21 days. Tumor assessments were performed every 3 months. Results: As of 8 November 2013, 58 received PoV + RTX (38 DLBCL; 20 FL), 63 PiV + RTX (42 DLBCL; 21 FL). Median prior therapies [DLBCL, 3 (1-10); FL, 2 (1-8)] were balanced between treatment arms; 46% were RTX refractory. Median treatment (tx) cycles in DLBCL: 5 for both ADC (1-15); FL: 8.5 PoV (3-15) and 6 PiV (1-13). Overall safety profiles of both regimens were similar. Tx-emergent adverse events (AE) >25%: fatigue (52%), diarrhea (42%), nausea (37%), peripheral neuropathy (PN) (32%), constipation (26%). Grade ≥ 3 AE >3%: neutropenia (21%), diarrhea (6%), dyspnea (4%), febrile neutropenia (4%), hyperglycemia (4%) and PN (4%). Serious AE reported in 36%. Thirty-eight discontinued tx for AE after median 5 doses (range 1-14), including 16 for PN. Tx delays and ADC dose reductions reported in 27% and 22%. Two of 7 deaths (sepsis, urosepsis) unrelated to NHL were attributed to PiV. Complete (CR) and partial (PR) responses, n (%) [% 95% CI] (see Table). Conclusions: PoV and PiV + RTX were generally well-tolerated with similar toxicity. Neutropenia, PN and diarrhea were principal toxicities. Similar efficacy was observed with both ADCs in heavily pretreated pts with DLBCL. The higher CR rate with PoV + RTX suggests greater clinical activity in R/R FL. Combination studies of R + PoV with chemotherapy and with ADC schedules to reduce PN are ongoing or in planning. Clinical trial information: NCT01691898. PoV (CD79b) + RTX PiV (CD22) + RTX R/R DLBCL ORR CR PR N = 37 19 (51%) [34, 68] 5 (14%) [5, 29] 14 (38%) [23, 55] N = 37 20 (54%) [37, 71] 7 (19%) [8, 35] 13 (35%) [20, 53] R/R FL ORR CR PR N = 20 12 (60%) [36, 81] 6 (30%) [12, 54] 6 (30%) [12, 54] N = 21 14 (67%) [43, 85] 1 (5%) [0.1, 24] 13 (62%) [38, 82] Pharmacokinetic profiles were similar for both ADCs across DLBCL and FL with no free MMAE accumulation.