KEY TAKEAWAYS
- The phase 1b/2 study aimed to assess the safety of ViPOR for people with Relapsed/Refractory and Treatment-Naïve MCL.
- ViPOR × 6C treatment achieved high MRD-CR rates in various Mantle Cell Lymphoma (MCL) subgroups, showing safety across age groups.
Mantle Cell Lymphoma (MCL) remains incurable with standard chemotherapy. While oral targeted treatments show activity, they often lack strong responses alone and need prolonged use.
Researchers developed ViPOR, a safe multi-agent regimen, demonstrating lasting complete responses in refractory/recurrent B-cell lymphomas. In this study, they shared data specific to MCL from this ongoing ViPOR (NCT03223610) study. Patients with relapsed/refractory (R/R) and treatment-naive (TN) MCL meeting organ function criteria participated.
Phase 1 involved R/R patients receiving two Venetoclax (VEN) doses (200 and 400 mg) to determine the recommended phase 2 dose (RP2D). The treatment involved VEN orally from Day 2 to Day 14 in Cycles 2-6, beginning with a 12-day inpatient dose increase in Cycle 2. This was alongside fixed-dose Ibrutinib, Prednisone, Obinutuzumab, and Lenalidomide.
In Phase 2, both R/R and TN MCL patients received treatment at the RP2D without a maintenance phase. Patients received preventive measures for tumor lysis syndrome (TLS), granulocyte colony-stimulating factor (G-CSF), and Pneumocystis pneumonia (PCP), while venous thromboembolism (VTE) prevention was at the physician’s discretion. Assessments included imaging and MRD monitoring.
Twenty-four patients diagnosed with MCL, comprising 11 relapsed/refractory (R/R) and 13 TN, were enrolled. The majority were male, with a median age of 67 years (ranging from 41 to 82). Specific characteristics included blastoid morphology in 29%, Ki-67 ≥30% in 38%, and TP53 mutations in 26% of patients.
In the R/R group, the median number of prior treatments was 3 (ranging from 1 to 4), with 45% previously treated with BTK inhibitors and 73% refractory to their last treatment.
No dose-limiting toxicities (DLTs) were observed, and VEN at a 400 mg dose was used in Phase 2. The most common adverse events were related to blood disorders, notably thrombocytopenia (17%), anemia (9%), and neutropenia (9%), without febrile neutropenia among 126 cycles.
Notable non-blood-related Grade 3 adverse events in over 10% of patients included hypokalemia (22%). Diarrhea (65%) and rash (52%) were the most common non-blood-related adverse events. Serious atrial fibrillation occurred in two patients, and one patient experienced a serious venous thromboembolism (VTE).
No tumor lysis syndrome (TLS) or treatment-related mortality was reported. Dose reductions were necessary in 25% of patients, while 86% completed the full treatment regimen of six cycles.
All 21 patients (100%) who discontinued treatment achieved complete remission (CR), encompassing various subgroups like blastoid, TP53 mutated, post-BTK inhibitor, and refractory patients. CRs were observed in all risk categories.
Follow-up showed that 78% of responses were still ongoing after a median duration of 17 months. The one-year time-to-progression (TTP), progression-free survival (PFS), and overall survival (OS) rates were 87%, 74%, and 80%, respectively.
The one-year TTP was 88% in relapsed/refractory patients, 90% in treatment-naive patients, 42% in blastoid subtype, and 67% in TP53 mutated MCL. Baseline circulating tumor DNA (ctDNA) was detected in 95% of patients, and 95% achieved molecular remission at the end of treatment.
The median duration of negative minimal residual disease (MRD) was 6 months. Of the three patients who experienced relapse after achieving CR, all showed molecular relapse before imaging, with an average lead time of 4 months.
ViPOR treatment, lasting six cycles without ongoing therapy, achieved significant MRD-CRs in diverse MCL cases. When combined with G-CSF, ViPOR showed safety in MCL patients of all ages without severe complications like TLS or febrile neutropenia.
Source: https://onlinelibrary.wiley.com/doi/full/10.1002/hon.3164_437
Clinical Trial: https://clinicaltrials.gov/study/NCT03223610
Melani, C.J., Lakhotia, R., Pittaluga, S., Phelan, J.D., Yang, Y., Davies-Hill, T., Simard, J., Muppidi, J., Huang, D.W., Thomas, C.J., Ceribelli, M., Tosto, F.A., Pradhan, A., Juanitez, A.M., Rimsza, L.M., Jacob, A., Simmons, H., Steinberg, S.M., Jaffe, E.S., Staudt, L.M., Roschewski, M. and Wilson, W.H. (2023), Venetoclax, ibrutinib, prednisone, obinutuzumab, and lenalidomide (ViPOR) in relapsed/refractory (R/R) and treatment-naïve (TN) mantle cell lymphoma (MCL). Hematological Oncology, 41: 582-584. https://doi.org/10.1002/hon.3164_437
