Rituximab is a chimeric, anti-CD20 monoclonal antibody initially approved for relapsed, refractory indolent B-cell non-Hodgkin's lymphoma (NHL), and is being applied in an increasing variety of clinical scenarios. Most adverse events are due to an infusion-related symptom complex, and severe pulmonary complications are rare. We describe a case of an NHL patient who received rituximab and developed symptomatic, biopsy-proven multinodular bronchiolitis obliterans with organizing pneumonia (BOOP). This is the first reported case of BOOP associated with single-agent rituximab, and along with two other patients we describe, as well as two prior reports of BOOP in NHL patients receiving rituximab-based combinations, strengthens the possibility of a causal relationship. Moreover, these findings suggest that the incidence of BOOP following rituximab therapy may be higher than has been previously appreciated. Physicians utilizing rituximab should be aware of this association given the difficulty of differentiating between presentations of BOOP and neoplastic pulmonary processes.

A phase I study of a combination of the proteasome inhibitor bortezomib and pegylated liposomal doxorubicin showed significant anti-tumor activity against advanced multiple myeloma, with 36% of patients achieving a complete or near-complete response and 73% having a partial response or better. Given this encouraging efficacy, it was therefore of interest to update the prior experience and define parameters such as time to progression, time to retreatment, and overall survival. Additional follow-up was collected on all evaluable multiple myeloma patients and revealed a median time to progression of 9.3 months versus 3.8 months on whatever had been the patient's prior therapy. Time to retreatment was prolonged from 5.9 months after the patient's prior therapy to 24.2 months after bortezomib with pegylated liposomal doxorubicin. The median overall survival after therapy with bortezomib and pegylated liposomal doxorubicin was 38.3 months. These findings compare favorably with results reported for bortezomib alone and support the possibility that the bortezomib/pegylated liposomal doxorubicin regimen may provide superior efficacy against relapsed/refractory multiple myeloma.

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7617 Background: Preclinical studies of bortezomib (bort) with pegylated liposomal doxorubicin (PLD) showed enhanced anti-tumor efficacy compared with either single agent. This led to a phase I trial in patients (pts) with advanced hematologic malignancies who received bort on days 1, 4, 8 and 11 at 0.9–1.5 mg/m2, and PLD on day 4 at 30 mg/m2, every three weeks (Blood 105:3058, 2005). Significant activity was seen, with 36% of relapsed/refractory multiple myeloma (MM) pts achieving a complete or near-complete response, while 73% attained at least a partial response. It was therefore of interest to define time to progression (TTP) and overall survival (OS) with this regimen. Methods: Additional follow-up was obtained on all 22 evaluable MM pts. TTP and OS were determined from day 1 of bort/PLD, and the Kaplan-Meier method was used to calculate time-to-event estimators. The log-rank test was used to compare TTP and time to retreatment (TTR) on bort/PLD vs. the prior therapy. Cox regression was used to evaluate covariates for association with TTP and OS. Results: Median TTP with bort/PLD was 9.3 months (mos)(95% confidence interval (CI) 8.3–22.4) versus 3.8 mos (95% CI 2.3–10.0) on the pt’s prior therapy (p=0.04). Similarly, the median TTR after bort/PLD was prolonged (p=0.04) compared with TTR after the prior regimen, with 3 pts having not yet received their next therapy. With a median follow-up of 36 mos, 13 of these patients (59%) remain alive, and the median OS has not yet been reached. Karnofsky performance status was significantly associated with TTP (p=0.02), while the hematocrit (hct; p=0.06) and IgA subtype (p=0.08) had borderline significance. Hct was significantly associated with OS (p=0.03), while the number of prior regimens (p=0.07) and the platelet count (p=0.06) had borderline significance. Conclusions: Bort alone induced a median TTP of 6.6 mos and OS of 16 mos in MM (N Engl J Med 348: 2609, 2003). The current results support the possibility that the bort/PLD regimen may improve upon TTP, and especially OS, compared with bort alone. This hypothesis is being studied in a randomized, international phase 3 trial ( NCT00103506 ) comparing bort and bort/PLD. No significant financial relationships to disclose.