Phase II Results Show Activity of Polatuzumab Vedotin Combination in DLBCL

The CD79b-targeting antibody drug conjugate polatuzumab vedotin, in combination with rituximab, cyclophosphamide, doxorubicin, and prednisone (R-CHP), was able to be administered safely in patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL) in an initial, phase Ib/II dose-escalation study. Results from the phase II portion of the trial were presented at the 22nd Congress of the European Hematology Association, and investigators reported that the combination “produced promising response rates” in this patient population.

Hervé Tilly, MD, from Centre Henri Becquerel at the University of Rouen in France, and colleagues evaluated the combination treatment in 45 patients (median age = 69 years; range not provided): five patients from the dose-escalation phase and 40 from the dose-expansion phase.

Most patients (93%) were >60 years old with stage III/IV disease (82%) and an International Prognostic Index (IPI) score of three to five (78%). “The majority of the patients in this trial represented a poor prognosis group [based on] age and IPI [score],” the authors noted.

Per the phase Ib/II trial’s protocol, all patients had previously untreated, newly diagnosed DLBCL and received six or eight 21-day cycles of polatuzumab vedotin 1.8 mg/kg (the recommended phase II dose) plus R-CHP at standard doses:

  • cyclophosphamide 750 mg/m2 intravenously (IV) every 3 weeks
  • doxorubicin 50 mg/m2 IV every 3 weeks
  • prednisone 100 mg orally once-daily for 5 days every 3 weeks
  • rituximab 375 mg/m2 IV every 3 weeks

All patients received at least one dose of the study drug, and most completed six (n=23) or eight (n=17) cycles.

All patients experienced at least one adverse event (AE), and grade 3/4 AEs occurred in 58 percent of patients. The most common grade 3/4 AEs included neutropenia (27%) and febrile neutropenia (27%). Serious AEs were reported in 17 patients (38%), the most common being febrile neutropenia and neutropenia, while one patient experienced grade 5 atrial fibrillation.

Peripheral neuropathy occurred in 18 patients (40%), mostly grade 1 (n=12). The authors noted that all cases of grade 2/3 peripheral neuropathy occurred during or after the fifth treatment cycle.

Six patients required dose reductions of polatuzumab vedotin and one patient required a dose reduction of cyclophosphamide and doxorubicin. Overall, four patients discontinued polatuzumab vedotin (related to the grade 5 atrial fibrillation, peripheral neuropathy, E. coli urinary tract infection, and worsening essential tremor).

After patients completed six or eight treatment cycles, the overall response rate (assessed by positron emission tomography) for 44 evaluable patients was 91 percent, including a complete response (CR) rate of 78 percent and a partial response rate of 13 percent. Three patients’ disease progressed.

Of the 29 patients with gene-expression data available, the cell of origin was germinal center B cell-like (GCB) in 48 percent of cases (n=14), activated B cell-like (ABC) in 38 percent (n=11), and unclassified in 14 percent (n=4). In this cohort, 91 percent of patients with ABC DLBCL and 86 percent of patients with GCB DLBCL achieved CR. At data cutoff (November 4, 2016), after a median duration of 9.5 months (range = 1.3-28 months), one patient’s disease had progressed, the authors reported.

The study’s findings are limited by its small patient population and non-randomized design.

Dr. Tilly reports receiving honoraria and travel/accommodation expenses from Roche Pharma.


Reference

Tilly H, Sharman J, Bartlett N, et al. POLA-R-CHP: polatuzumab vedotin combined with rituximab, cyclophosphamide, doxorubicin, prednisone for patients with previously untreated diffuse large B-cell lymphoma. Abstract #S106. Presented at the 22nd Congress of the European Hematology Association, June 23, 2017; Madrid, Spain.

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