Herpes Zoster (HZ) Complicating Bortezomib Therapy of Relapsed/Refractory Indolent B-Cell and Mantle Cell Lymphoma: An Analysis of Two Phase II Trials.

The use of bortezomib-based therapy is known to be associated with an increased risk of HZ in patients (pts) with multiple myeloma, who have disease-related inherent immune defects. A 13% incidence of HZ occurrence in pts with relapsed/refractory MM who received single agent bortezomib has been previously reported (J Clin Oncol 2008; 26:4784-4790). However, the occurrence of HZ in bortezomib-treated pts with non-Hodgkin lymphoma (NHL) has not been previously examined.

We reviewed clinical data from two phase II trials in which bortezomib therapy was administered to pts with relapsed/refractory mantle cell NHL or indolent B-cell NHL. The occurrence of HZ complicating their treatment course was delineated, and an analysis for potential predisposing risk factors was undertaken.

A total of 236 relapsed/refractory pts, median age 65 years (yrs), enrolled on these trials was examined. Mantle cell NHL pts (n=155) received single-agent bortezomib, 1.3 mg/m², days (D) 1, 4, 8, 11, 21-D cycles; those with indolent B-cell NHL (n=81) received either bortezomib, 1.3 mg/m², D 1, 4, 8, 11, 21-D cycles, plus rituximab, 375 mg/m², D 1, 8, 15 (cycle 1) and D 1 (cycle 2) (n=41), or bortezomib, 1.6 mg/m², D 1, 8, 15, 22, 35-D cycles, and rituximab, 375 mg/m², D 1, 8, 15, 22 (cycle 1) (n=40). HZ occurred in 24 pts (10.2%) overall, with a comparable incidence in both disease subgroups. Median time to HZ occurrence was 39 (range, 11–206) days (< 2 cycles). Overall, 11% of pts had had a prior episode of HZ. Baseline demographic and clinical variables were examined, including age, gender, disease stage, baseline absolute neutrophil and lymphocyte counts, hemoglobin, lactate dehydrogenase, prior HZ, and number and types of prior therapies, to determine if any may predict for subsequent development of HZ. With regard to age, 71% of pts with HZ were age ≥65 yrs, compared to 48% without HZ (p=0.03). 63% of pts with HZ had received ≥2 lines of prior therapy, compared to 47% in those without HZ (p=0.15). 4% of pts with HZ had undergone prior stem cell transplantation, compared to 13% of pts without HZ. Of the pts with HZ, 25% had received prior purine analog therapy, compared to 9% of pts without HZ. The other baseline variables had no impact on the occurrence of HZ. In the 77 pts who responded to bortezomib protocol therapy (complete/partial responses), the incidence of HZ was 14%, compared to an 8% incidence of HZ in the 159 non-responders (p=0.15).

HZ may complicate the course of relapsed/refractory indolent or mantle cell NHL pts receiving bortezomib-based therapies, with an incidence similar to the myeloma population. Pts who are elderly, more heavily-pretreated, or have received prior purine analog therapy may be at greater risk of this complication, and should be strongly considered for antiviral prophylaxis during such therapy.

Morrison:Merck: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Speakers Bureau; Amgen: Consultancy, Speakers Bureau; Genentech: Speakers Bureau; Pfizer: Speakers Bureau. Off Label Use: Discussion of Velcade in NHL subtypes other than mantle cell lymphoma is included. Fisher:Allos Therapeutics: Consultancy; CytoKinetics: Consultancy; GSK: Consultancy; MundiPharma: Consultancy; Seattle Genetics: Consultancy; Millennium Pharmaceuticals, Inc,: Consultancy. Goy:Millennium, Celgene, GSK and Genentech: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Bernstein:Millennium Pharmaceuticals, Inc: Consultancy, Honoraria, Speakers Bureau. Boral:Millennium Pharmaceuticals, Inc.: Employment; Takeda Pharmaceuticals: Equity Ownership. Neuwirth:Millennium Pharmaceuticals, Inc.: Employment.