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).
Transcript
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.
The ASCO Post Staff
Tycel J. Phillips, MD, of the City of Hope National Medical Center, discusses data that showed fixed-duration glofitamab monotherapy induced high and durable complete response rates in patients with mantle cell lymphoma (MCL) who received obinutuzumab pretreatment. This is one of the largest data sets and longest follow-ups reported with a CD20/CD3 bispecific monoclonal antibody for patients with relapsed or refractory MCL (Abstract 74).
The ASCO Post Staff
Alex F. Herrera, MD, of the City of Hope National Medical Center, discusses results from the POLARIX study, which showed that circulating tumor DNA (ctDNA) analysis has prognostic value for patients with previously untreated diffuse large B-cell lymphoma. Patients who did not achieve 2.5 or greater log-fold change and/or did not have ctDNA clearance following one cycle of polatuzumab vedotin along with rituximab, cyclophosphamide, doxorubicin, and prednisone had inferior outcomes than those who did. Early changes in ctDNA levels may be of use in risk-adapted trial designs to identify patients in need of alternative treatment. (Abstract 542).
The ASCO Post Staff
Abdul Rahman Al Armashi, MD, of Seidman Cancer Center, Case Western University, University Hospitals Cleveland Medical Center, discusses a retrospective analysis, using a CDC database, in one of the largest subgroup-based racial population studies analyzing mortality trends in patients with acute myeloid leukemia (AML). Between 2000 and 2019, AML mortality was the highest in Whites and the lowest in American Indians or Alaska Natives. The highest rate of increase in mortality was seen in Asians or Pacific Islanders. Dr. Al Armashi talks about the many variables that might contribute to these inequalities (Abstract 600).
The ASCO Post Staff
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.
The ASCO Post Staff
Paolo F. Caimi, MD, of the Taussig Cancer Institute, Cleveland Clinic, discusses new findings showing that patients with diffuse large B-cell lymphoma (DLBCL) who achieve a complete response after salvage therapy with rituximab, ifosfamide, carboplatin, and etoposide (R-ICE) can achieve long-term disease control, regardless of the time to relapse from initial therapy, particularly if they proceed to autologous stem cell transplant (ASCT). These results suggest that second-line chemotherapy followed by ASCT and/or CAR T-cell therapy for chemosensitive and chemorefractory patients may maximize patient outcomes, regardless of time to relapse (Abstract 156).
