Infections, Second Malignancies Risk Should be Considered in B-Cell Lymphoma

Treatment with bendamustine (Bendeka) and rituximab (Rituxan) carries a higher risk of infection and second primary malignancy than alternative therapies for patients with indolent B-cell lymphoma, according to findings from a retrospective analysis published in Hematological Oncology.

"In the future, treatment strategies that consider the risk of [secondary primary malignancy] after chemotherapy may be warranted for patients with [indolent B-cell lymphoma] with promising long‐term prognoses,” according to the authors of a retrospective analysis published in Hematological Oncology.

The analysis assessed several regimens including bendamustine plus rituximab (n = 2156), rituximab monotherapy (n = 780), as well as a cohort that received rituximab, cyclophosphamide, doxorubicin, vincristine (Oncovin), and prednisone (RCHOP); rituximab, cyclophosphamide, vincristine, and prednisone (RCVP); or rituximab, cyclophosphamide, pirarubicin, vincristine, and prednisone (RTHPCOP; n = 2298).

The 5-year cumulative incidence function of secondary primary malignancy was 18.1% among patients treated with bendamustine plus rituximab vs 12.5% among those treated with rituximab monotherapy (P <.01) and 12.9% among those treated with RCHOP/RCVP/RTHPCOP (P <.0001). Incidence was also higher with bendamustine plus rituximab than RCHOP/RCVP/RTHPCOP in the Fine-Gray subdistribution hazards model (subhazard ratio, 1.33; 95% CI, 1.10-1.61).

Additionally, a nested case‐control study using an entire cohort produced results that were consistent with the aforementioned findings. Higher odds of a secondary primary malignancy were associated with frontline (OR 1.43; 95% CI, 1.14-1.78), post-frontline (OR 1.26; 95% CI, 0.96-1.64), and any‐line bendamustine (OR 1.33; 95% CI, 1.09-1.62).

There was no difference in overall survival between the RCHOP/RCVP/RTHPCOP and bendamustine plus rituximab groups after propensity score matching.

“This real‐world data analysis of first‐line chemotherapy among patients with [indolent B-cell lymphoma] provides additional information on [bendamustine plus rituximab]–associated second primary malignancies and the characteristics of infectious complications after [indolent B-cell lymphoma] chemotherapy,” the investigators wrote. “Active surveillance for [a second primary malignancy] and careful monitoring of cytomegalovirus infection are warranted in patients treated with [bendamustine/rituximab], while pneumocystis pneumonia prophylaxis should be enriched in patients treated with RCHOP/RCVP/RTHPCOP.”

The retrospective observational study assessed health care records from the Medical Data Vision Co., Ltd. database from April 2009 to April 2020. The estimated median number of 6-month chemotherapy cycles was 6 for the bendamustine regimen, 4 for rituximab monotherapy, 6 for RCHOP/RCVP/RTHPCOP.

The median ages in the 3 treatment groups ranged from 66 to 70 years old. Women comprised the majority of the rituximab monotherapy (54.5%) and RCHOP/RCVP/RTHPCOP (52.0%) cohorts and a minority (47.9%) of the bendamustine group. Most patients in across all groups—ranging from 71.5% to 87.0%—had follicular lymphoma compared with mantle cell, marginal zone, or lymphoplasmacytic lymphoma.

Among the total patient population (n = 5234), observed infections included bacterial pneumonia infections (8.5%), instances of pneumocystis pneumonia (0.9%), herpes zoster infections (3.1%), and cytomegalovirus infections (1.1%).

Compared with rituximab monotherapy (4.6%; 0.5%), bacterial pneumonia and herpes zoster infections, respectively, were more frequent in patients receiving RCHOP/RCVP/RTHPCOP (10.7%; 3.5%) and bendamustine/rituximab (7.6%; 3.5%). Additionally, pneumocystis pneumonia was more frequent with RCHOP/RCVP/RTHPCOP (1.5%), and cytomegalovirus infections were more frequent with the bendamustine regimen (2.4%).

Investigators identified an association between bendamustine and an increased risk of cytomegalovirus infection, and RCHOP/RCVP/RTHPCOP with an increased risk of bacterial pneumonia and pneumocystis pneumonia.

“In the future, treatment strategies that consider the risk of [secondary primary malignancy] after chemotherapy may be warranted for patients with [indolent B-cell lymphoma] with promising long‐term prognoses,” the investigators concluded.

Reference

Dote S, Inose R, Goto R, Kobayashi Y, Muraki Y. Risk of a second cancer and infection in patients with indolent B-cell lymphoma exposed to first-line bendamustine plus rituximab: A retrospective analysis of an administrative claims database. Hematol Oncol. 2023;10.1002/hon.3128. doi:10.1002/hon,3128