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Bortezomib plus VR-CAP looks promising in untreated MCL

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

Key clinical point: First-line bortezomib therapy significantly improves overall survival in patients with newly diagnosed mantle cell lymphoma.

Major finding: Median overall survival was 90.7 months in the intervention arm (bortezomib in addition to rituximab plus chemotherapy) versus 55.7 months in the control arm (hazard ratio, 0.66; 95% confidence interval, 0.51-0.85; P = .001).

Study details: LYM-3002 was a phase 3, randomized, open-label study of 487 transplant-ineligible patients with untreated mantle cell lymphoma.

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

Read the article.

Citation:

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

Commentary:

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.

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