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First-line bortezomib prolongs survival in MCL

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Bortezomib plus VR-CAP is a “substantial advance”

The proteasome inhibitor, bortezomib, represents a “substantial advance” for the treatment of newly diagnosed mantle cell lymphoma, according to Simon Rule, MD.

In an accompanying commentary, he stated that bortezomib-based VR-CAP (rituximab plus cyclophosphamide, doxorubicin, and prednisone) showed a clear survival benefit in the LYM-3002 trial, compared with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). However, in order to use this combination in elderly patients, the administration method must be considered. Additionally, it makes sense to routinely use rituximab maintenance.

While the final analysis of the LYM-3002 trial is positive, there are caveats to consider before changing practice, particularly for elderly patients. First, the study had a somewhat younger population and fewer high-risk patients, compared with the only similar study of R-CHOP regimen in an elderly population. The bortezomib plus VR-CAP combination also had significant toxicity that could limit its widespread use in elderly patients.

Dr. Rule also noted that, internationally, bendamustine-based therapy is increasingly being chosen over R-CHOP for older patients with mantle cell lymphoma.

“Whether VR-CAP or the combination of bortezomib and bendamustine-based regimens will be the optimal approach has yet to be established. However, if R-CHOP is being considered, then the long-term survival results reported by Robak and colleagues strongly support the use of VR-CAP as an alternative,” Dr. Rule wrote.

Dr. Rule is with the University of Plymouth (England). These comments are adapted from his commentary (Lancet Oncol. 2018 Oct 19. doi: 10.1016/S1470-2045[18]30743-5). Dr. Rule reported receiving grants and personal fees from Janssen Pharmaceuticals.



Bortezomib in combination with rituximab plus chemotherapy significantly improved overall survival in transplant-ineligible patients with newly diagnosed mantle cell lymphoma (MCL), compared with standard treatment, according to final results from the international, phase 3 LYM-3002 trial.

Intermediate magnification micrograph of mantle cell lymphoma of the terminal ileum. Courtesy Wikimedia Commons/Nephron/Creative Commons

Intermediate magnification micrograph of mantle cell lymphoma of the terminal ileum.

After a median follow-up period of 82.0 months, median overall survival was 90.7 months among participants who were given first-line bortezomib in addition to rituximab plus cyclophosphamide, doxorubicin, and prednisone (VR-CAP) versus 55.7 months in the control arm, where patients were given rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP), for a hazard ratio of 0.66 (95% confidence interval, 0.51-0.85; P = .001).

Tadeusz Robak, MD, of the Medical University of Lodz in Poland, and his colleagues also reported that patients in the bortezomib arm experienced two novel adverse effects, which were different from findings reported in the primary analysis. Each case was classified as grade 4; there was one case of gastric cancer and one case of lung adenocarcinoma.

The findings were reported in the Lancet Oncology.

Among 268 patients in the follow-up analysis set, the median age was 66 years and 31% were classified as high risk based on the MCL-specific International Prognostic Index (MIPI). For those considered high risk, no significant difference was noted when comparing the two groups on the basis of overall survival.

“When analyzed according to MIPI risk category, VR-CAP was associated with significantly improved overall survival, compared with R-CHOP in the low-risk and intermediate-risk categories, but not in the high-risk category,” the investigators wrote.

The authors acknowledged a key limitation of the study was that rituximab was not given as a maintenance therapy since it was not considered standard of care at the time of study initiation.

Moving forward, Dr. Robak and his colleagues recommended that bortezomib be investigated in combination with newer targeted therapies in order to establish best practice for treating MCL.

The study was sponsored by Janssen Pharmaceuticals. The authors reported financial ties to Janssen, Celgene, Ipsen Biopharmaceuticals, Johnson & Johnson, Novartis, and others.

SOURCE: Robak T et al. Lancet Oncol. 2018 Oct 19. doi: 10.1016/S1470-2045(18)30685-5.

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