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
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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
Paul G. Richardson, MD, of the Dana-Farber Cancer Institute, discusses preliminary results from the dose-expansion phase of the CC-92480-MM-001 Trial, which showed promising efficacy in patients with relapsed and refractory multiple myeloma, including those with prior BCMA-targeted therapies. Patients in these two groups had an overall response rate of 40% and 50%, respectively. The results support the development of mezigdomide, currently being evaluated in combination with standard therapies in multiple myeloma as part of a large, ongoing phase I/II trial (NCT03989414) and planned phase III studies (Abstract 568).
The ASCO Post Staff
Julie Côté, MD, of CHU de Québec–Université Laval, discusses findings from the Canadian Myeloma Research Group database, which showed that integrating bortezomib and lenalidomide into the autologous stem cell transplant (ASCT) sequence produces a median overall survival rate ≥ 10 years in most patients with newly diagnosed multiple myeloma. These observations highlight the contribution of post-ASCT maintenance, particularly lenalidomide given until disease progression, when used in multiple patient groups including those with and without high risk, as well as those requiring a second induction regimen (Abstract 117).
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
Joseph Schroers-Martin, MD, of Stanford University, discusses immunogenomic features reflecting divergent biology in posttransplant lymphoproliferative disorders (PTLD). These include evidence of mismatch repair defects in Epstein-Barr virus–positive PTLD, tumor microenvironment depletion, and MYC pathway enrichment in certain patients (Abstract 72).
The ASCO Post Staff
Anand P. Jillella, MD, of Georgia Cancer Center at Augusta University, discusses results from the ECOG-ACRIN EA9131 Trial, which showed that using a simplified treatment algorithm and management recommendations made by a group of specialists, resulted in a dramatic improvement in 1-year survival of patients with acute promyelocytic leukemia (Abstract 421).