VR-CAP improved duration and quality of response in newly-diagnosed MCL patients over R-CHOP

In February, in the journal Haematologica, Gregor Verhoef from the University Hospital Leuven, Leuven, Belgium, and colleagues published a post-hoc analysis study of the multi-center, international, randomized, phase III LYM-3002 study comparing R-CHOP to VR-CAP. The study recruited patients who were newly diagnosed with MCL but ineligible or not considered for stem cell transplantation. The purpose of the post-hoc analysis was to study the relationship between outcome, response, and response quality in patients treated with R-CHOP or VR-CAP. Patients were stratified according to response classification, Complete Response (CR/CRu) and Partial Response (PR), and by MIPI risk status.

Key Highlights:

• Recruited 487 pts (R-CHOP = 244pts, VR-CAP = 243pts)
• Total 457 pts evaluable (R-CHOP = 228pts, VR-CAP = 229pts)
• Six 21-day cycles of either:
  • R-CHOP = 375mg/m² rituximab, 750mg/m² cyclophosphamide, 50mg/m² doxorubicin, 1.4mg/m² vincristine on D1, 100mg/m² prednisone on D1–5
  • VR-CAP = 1.3mg/m² bortezomib on D1, 4, 8, 11, then 375mg/m² rituximab, 750mg/m² cyclophosphamide, 50mg/m² doxorubicin, 1.4mg/m² on D1, 100mg/m² prednisone on D1–5
• Results:
  • Median PFS CR/CRu pts: R-CHOP = 19.8 months, VR-CAP = 40.9 months
  • Median PFS PR pts: R-CHOP = 11.7 months, VR-CAP = 17.1 months
  • Median Time To Next Treatment (TTNT) in CR/CRu pts: R-CHOP = 26.6 months, VR-CAP = not evaluable
  • Median TTNT in PR pts: R-CHOP = 24.3 months, VR-CAP = 35.3 months
  • Median DoR in CR/CRu pts: R-CHOP = 18.5 months, VR-CAP = 42.1 months
  • Median DoR in PR pts: R-CHOP = 9.6 months, VR-CAP = 20.2 months
• In CR/CRu and PR pts, longer PFS, TTNT, and DoR with VR-CAP versus R-CHOP was greatest in low-risk and intermediate-risk MIPI groups pts
• Median time to first response was similar in both treatment groups
• Analysis of lymph node lesion size changes versus baseline CT results indicated reduction in size of all lesions to below 0mm x 0mm (‘too small to measure’) in:
  • In CR/CRu pts: R-CHOP = 59%, VR-CAP = 72% pts
  • In PR pts: R-CHOP = 28%, VR-CAP = 48%
  • Longer PFS observed in pts who had reductions to measurable lymph node lesion size vs those who had at least one measurable lesion after treatment in CR and PR groups

In conclusion, the authors stated that VR-CAP resulted in an improved duration, and quality, of response than R-CHOP, which became more obvious in patients with low- or intermediate-risk MIPI. Furthermore, they state that their data showed that disease elimination, as measured in this study by lymph node lesion size reduction, is potentially a better predictor of outcome than type of response. The authors also suggest that the addition of maintenance rituximab to the VR-CAP treatment regimen could potentially extend the PFS of some patients.

Abstract:

In the phase III LYM-3002 study comparing intravenous VR-CAP with R-CHOP in patients with newly-diagnosed, measurable stage II-IV mantle cell lymphoma, not considered, or ineligible for, transplant, median progression-free survival was significantly improved with VR-CAP (24.7 vs R-CHOP 14.4 months; P<0.001). This post-hoc analysis evaluated the association between the improved outcomes and quality of responses achieved with VR-CAP versus R-CHOP in LYM-3002. Patients were randomized to 6-8 21-day cycles of VR-CAP or R-CHOP. Outcomes included progression-free survival, duration of response (both IRC assessed), and time-to-next anti-lymphoma treatment, evaluated by response (complete response/unconfirmed complete response and partial response), MIPI risk status, and maximum reduction of lymph-node measurements expressed as the sum of the product of the diameters. Within each response category, median progression-free survival by independent review committee was longer for patients receiving VR-CAP versus R-CHOP who achieved complete response/unconfirmed complete response (40.9 vs 19.8 months) compared with those achieving partial response (17.1 vs 11.7 months); similarly, for median time-to-next anti-lymphoma treatment (complete response/unconfirmed complete response: not evaluable vs 26.6 months; partial response: 35.3 vs 24.3 months). Within the complete/unconfirmed complete and partial response categories, progression-free survival, duration of response and time-to-next anti-lymphoma treatment were more pronounced in patients with low- and intermediate-risk MIPI with VR-CAP versus R-CHOP. In each response category, more VR-CAP than R-CHOP patients had a sum of the product of the diameters nadir of 0 during serial radiological assessments. Results of this post-hoc analysis suggest a greater duration and quality of response in VR-CAP versus R-CHOP patients, which was more evident in patients with low- and intermediate-risk MIPI.