Eva Hoster, PhD, on Mantle Cell Lymphoma: Predictive Value of Minimal Residual Disease on Efficacy of Rituximab Maintenance
2022 ASH Annual Meeting and Exposition
Eva Hoster, PhD, of Munich University, discusses results from the European MCL Elderly Trial, which confirmed the strong efficacy of rituximab maintenance in minimal residual disease (MRD)-negative patients with mantle cell lymphoma (MCL) after induction. Omitting maintenance based on MRD-negativity is thus discouraged. Considering the short time to progression, more effective treatment strategies should be explored in MRD-positive patients to improve long-term prognosis (Abstract 544).
Disclaimer: This video transcript has not been proofread or edited and may contain errors.
Rituximab maintenance has become standard of care in the first line treatment of mantle cell lymphoma. The European MCL Elderly Trial has established rituximab maintenance after R-CHOP in older patients with mantle cell lymphoma. We assessed and analyzed MRD as part of the MCL Elderly Trial to investigate whether the MRD status at end of induction predicts the efficacy of rituximab maintenance and to find trigger points for MRD based treatment guidance.
The European MCL Elderly Trial recruited patients with previously untreated and advanced stage mantle cell lymphoma older than 60 years and not suitable for autologous stem cell transplantation. Patients were first randomized between six cycles of R-FC and eight cycles of R-CHOP and responding patients were subsequently randomized between rituximab and interferon maintenance until progression. Minimal residual disease or MRD was assessed by real-time quantitative PCR according to standardized guidelines reaching a target sensitivity of 10 to the -5 and MRD time points were at mid-induction, end of induction and the two monthly intervals during maintenance and follow up. MRD assessment was possible and 80% of patients screened for a molecular marker and tumor dissemination enhanced the identification of a molecular marker. Induction with R-FC resulted in a deeper and more rapid MRD clearance compared with R-CHOP. And of note, the differences observed in MRD response were much larger than those seen for clinical remission.
The efficacy of rituximab maintenance was clearly confirmed in patients MRD negative at end of induction and this was especially seen in patients pre-treated with R-CHOP. In contrast, in MRD positive patients at end of induction, the efficacy of rituximab maintenance seemed potentially reduced. In the two years after end of induction rituximab maintenance was associated with more frequent, constant MRD negativity and conversions to MRD negativity and less frequent conversions to MRD positivity. MRD positivity after end of induction and start of maintenance was associated with relatively short response duration and medium times from MRD positivity to clinical relapse and were rather short with around one to one and a half years.
In conclusion, our results confirm the strong efficacy of rituximab maintenance in MRD negative patients which means that omitting rituximab maintenance in MRD negative patients is clearly discouraged by our results. MRD positivity after end of induction inside of maintenance seems to be an important trigger point for treatment intensification or novel treatment approaches. And these MRD guided treatment strategies should be studied in future clinical trials.
Irene Roberts, MD, of Oxford’s Weatherall Institute of Molecular Medicine, discusses children with Down syndrome, who have a more than 100-fold increased risk of developing acute myeloid leukemia before their fourth birthday compared to children without Down syndrome. Their risk of acute lymphoblastic leukemia is also increased by around 30-fold. Dr. Roberts details current knowledge about the biologic and molecular basis of this relationship between leukemia and Down syndrome, the role of trisomy 21 in leukemogenesis, and the clinical implications of these findings.
Jiye Liu, PhD, of Dana-Farber Cancer Institute, discusses study findings that demonstrate KDM6A regulates CD38 and CD48 expression in multiple myeloma. Dr. Liu’s team validated combination treatment with an FDA-approved EZH2 inhibitor plus daratumumab, which can overcome daratumumab resistance in preclinical multiple myeloma models, providing the rationale for combination clinical trials to improve patient outcome (Abstract 148).
Jia Ruan, MD, PhD, of Meyer Cancer Center, Weill Cornell Medicine, and NewYork-Presbyterian Hospital, discusses trial results demonstrating that the triple chemotherapy-free combination of acalabrutinib, lenalidomide, and rituximab is well tolerated, highly effective, and produces high rates of minimal residual disease (MRD)-negative complete response as an initial treatment for patients with mantle cell lymphoma, including those with TP53 mutations. Real-time MRD analysis may enable treatment de-escalation during maintenance to minimize toxicity, which warrants further evaluation. An expansion cohort of acalabrutinib/lenalidomide/obinutuzumab is being launched (Abstract 73).
Jorge E. Cortes, MD, of Georgia Cancer Center at Augusta University, discusses new findings on vodobatinib, which was administered to patients with chronic-phase Philadelphia chromosome–positive chronic myeloid leukemia (CML) and appeared to be efficacious and safe in people who had received therapy with two or three prior tyrosine kinase inhibitors (TKIs). Vodobatinib remains a potential option for these highly refractory patients. A phase II study (NCT02629692) of vodobatinib is ongoing in CML patients whose disease has failed to respond to three or more TKIs, including ponatinib (Abstract 84).
Jennifer R. Brown, MD, PhD, of Dana-Farber Cancer Institute, discusses phase III findings of the ALPINE study, which showed that zanubrutinib is more efficacious and better tolerated than ibrutinib as a treatment for patients with relapsed or refractory chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL). In this first head-to-head comparison of the two BTK inhibitors, the superior progression-free survival of zanubrutinib was observed across all major subgroups, including high-risk patients (Abstract LBA-6).