Contributions
Abstract: EP790
Type: E-Poster Presentation
Session title: Indolent and mantle-cell non-Hodgkin lymphoma - Clinical
Background
Around 5-10% of mantle cell lymphoma (MCL) patients are primary refractory to chemotherapy. They have an extremely dismal prognosis, similar to responsive patients that relapsed within 12 months. Despite better understanding of risk factors and evolving classifications, these scores could not predict all high-risk patients and were not designed to guide treatment strategy in newly diagnosed MCL.
Aims
We conducted an ancillary study in a prospective phase III trial randomizing observation versus Rituximab maintenance after R-DHAP followed by ASCT (NCI NCT00921414; LyMa Trial; Le Gouill et al, NEJM 2017). Herein, we report our study of high-risk MCL patients.
Methods
High-risk MCL patients were defined as being primary chemo-refractory or having relapsed within 12 months following randomization (Visco BJH 2018; Eskelund ICML 2019). Patient's characteristics at baseline, treatment at relapse and outcomes were assessed. Survivals of high-risk versus control MCL patients were compared.
Results
Among the 299 MCL patients included in the LyMa trial, 31 high-risk MCL patients were identified (10.4%). Their characteristics at baseline were similar to control patients (n=268), regarding age, performance status, Ann Arbor staging, presence of B symptoms (p = NS). High-risk patients had more often elevated LDH (65% vs. 38%, p=0.006), high-risk MIPI score (45% vs. 16%, p < 0.001), Ki-67 > 30% (71% vs. 31%, p < 0.001) and blastoid/pleomorphic histology (32% vs. 9%, p < 0.001). In multivariate analysis, high-risk MIPI score and Ki-67 > 30% were associated with high-risk MCL. There was no significant difference in terms of TP53 expression between high-risk and control MCL. Many high-risk MCL patients have been classified as low-risk at diagnosis, with 36% of them having a low-risk MIPI score, 68% having a classic histology and 29% having a Ki-67 ≤ 30%. High-risk patients had more often positive MRD pre-ASCT in blood (47.1% vs. 20.6%, p=0.029) but not in the BM (50% vs. 34.9%, p=0.26) and had more positive PET pre-ASCT (48% vs. 25.6%, p=0.032). Median OS was 17 months in high-risk MCL patients, compared to 68 months in late progressors ((95% CI, 12 to 26 months vs. 47 to not reached respectively, p < 0.001). At relapse, 11/31 (36%) had a CNS involvement. Salvage therapies consisted of chemotherapy in 26 patients (CHOP, MTX-AraC, bendamustine, VR-CAP), rituximab in 26, temsirolimus in five, lenalidomide and combination of ibrutinib and lenalidomide in two other patients, as second line therapy. Ibrutinib was also used in two other patients as third line. Overall response rate was 37%, with 27% of complete response. Seven patients received allogeneic stem cell transplantation, of whom four died, from toxicity in two and from lymphoma in two. Median PFS and OS were 19.2 months and not reached for responding patients compared to 3.2 and 8.2 months for stable/progressive disease respectively.
Conclusion
Known risk factors do not perfectly identify high-risk MCL patients at baseline. High-risk patients with early disease progression had an extremely dismal prognosis and should receive innovative strategies combined with systematic CNS prophylaxis as salvage therapy.
Keyword(s): Mantle cell lymphoma, Refractory
Abstract: EP790
Type: E-Poster Presentation
Session title: Indolent and mantle-cell non-Hodgkin lymphoma - Clinical
Background
Around 5-10% of mantle cell lymphoma (MCL) patients are primary refractory to chemotherapy. They have an extremely dismal prognosis, similar to responsive patients that relapsed within 12 months. Despite better understanding of risk factors and evolving classifications, these scores could not predict all high-risk patients and were not designed to guide treatment strategy in newly diagnosed MCL.
Aims
We conducted an ancillary study in a prospective phase III trial randomizing observation versus Rituximab maintenance after R-DHAP followed by ASCT (NCI NCT00921414; LyMa Trial; Le Gouill et al, NEJM 2017). Herein, we report our study of high-risk MCL patients.
Methods
High-risk MCL patients were defined as being primary chemo-refractory or having relapsed within 12 months following randomization (Visco BJH 2018; Eskelund ICML 2019). Patient's characteristics at baseline, treatment at relapse and outcomes were assessed. Survivals of high-risk versus control MCL patients were compared.
Results
Among the 299 MCL patients included in the LyMa trial, 31 high-risk MCL patients were identified (10.4%). Their characteristics at baseline were similar to control patients (n=268), regarding age, performance status, Ann Arbor staging, presence of B symptoms (p = NS). High-risk patients had more often elevated LDH (65% vs. 38%, p=0.006), high-risk MIPI score (45% vs. 16%, p < 0.001), Ki-67 > 30% (71% vs. 31%, p < 0.001) and blastoid/pleomorphic histology (32% vs. 9%, p < 0.001). In multivariate analysis, high-risk MIPI score and Ki-67 > 30% were associated with high-risk MCL. There was no significant difference in terms of TP53 expression between high-risk and control MCL. Many high-risk MCL patients have been classified as low-risk at diagnosis, with 36% of them having a low-risk MIPI score, 68% having a classic histology and 29% having a Ki-67 ≤ 30%. High-risk patients had more often positive MRD pre-ASCT in blood (47.1% vs. 20.6%, p=0.029) but not in the BM (50% vs. 34.9%, p=0.26) and had more positive PET pre-ASCT (48% vs. 25.6%, p=0.032). Median OS was 17 months in high-risk MCL patients, compared to 68 months in late progressors ((95% CI, 12 to 26 months vs. 47 to not reached respectively, p < 0.001). At relapse, 11/31 (36%) had a CNS involvement. Salvage therapies consisted of chemotherapy in 26 patients (CHOP, MTX-AraC, bendamustine, VR-CAP), rituximab in 26, temsirolimus in five, lenalidomide and combination of ibrutinib and lenalidomide in two other patients, as second line therapy. Ibrutinib was also used in two other patients as third line. Overall response rate was 37%, with 27% of complete response. Seven patients received allogeneic stem cell transplantation, of whom four died, from toxicity in two and from lymphoma in two. Median PFS and OS were 19.2 months and not reached for responding patients compared to 3.2 and 8.2 months for stable/progressive disease respectively.
Conclusion
Known risk factors do not perfectly identify high-risk MCL patients at baseline. High-risk patients with early disease progression had an extremely dismal prognosis and should receive innovative strategies combined with systematic CNS prophylaxis as salvage therapy.
Keyword(s): Mantle cell lymphoma, Refractory