Selected prospective studies including ASCT in younger MCL patients
| Study/regimenauthor (ref) . | Key eligibility criteria . | Details of regimen . | Primary end point . | Patients . | Outcomes . |
|---|---|---|---|---|---|
| European Mantle Cell Lymphoma Network (MCL Younger): phase 3 study of R-CHOP vs R-CHOP alternating with R-DHAP → ASCT Hermine et al7 (2016) | Untreated MCL Age 18-65 y, stage II-IV, transplant eligible | Arm 1: R-CHOP × 6 cycles followed by HDT/ASCT Arm 2: R-CHOP alternating with R-DHAP followed by HDT/ASCT | Investigator-assessed TTF | n = 497 | TTF significantly longer in cytarabine group: median 9.1 y (95% CI, 6.3-not reached) vs control group: median 3.9 y (3.2-4.4); HR, 0.56; P = .038. 5-year TTF 65% vs 40%. No OS difference. |
| LYMA phase 3 study of R-DHAP → ASCT → rituximab maintenance vs other Le Gouill et al8 (2017) | Untreated MCL Age >65 y, stages II-IV, transplant eligible | Arm 1: R-DHAP (platinum derivative) × 4 cycles, if CR/PR then HDT/ASCT then rituximab maintenance every 2 mo for 3 y *If <CR/PR, then R-CHOP Arm 2: R-DHAP × 4 cycles, if CR/PR then HDT/ASCT then observation | EFS after ASCT | n = 257 | 4-year EFS was 79% (95% CI, 70-86) in the rituximab group vs 61% (95% CI, 51-70) in the observation group (P = .001) 4-year OS was 89% (95% CI, 81-94) in the rituximab group vs 80% (95% CI, 72-88) in the observation group (P = .04). |
| Second Nordic MCL study (MCL2): phase 2 study of R-maxi-CHOP alternating with R-HIDAC → ASCT Geisler et al10 (2008) Eskelund et al11 (2016) | Untreated MCL Age <66 y, stages II-IV, transplant eligible | R-maxi-CHOP alternating with R-high-dose cytarabine then HDT/ASCT *Pts in CR who converted from PCR-negative to PCR-positive were offered preemptive rituximab 375 mg/m2/wk for 4 weeks to prevent clinical relapse | OS, EFS, and PFS | n = 160 | 6-year OS, EFS, and PFS were 70%, 56%, and 66%, respectively. |
| GELA phase 2 study: R-CHOP × 3 followed by R-DHAP × 3 → ASCT Delarue et al12 (2013) | Untreated MCL Stage III-IV, transplant eligible Blastoid variants excluded | CHOP × 2, R-CHOP × 1, R-DHAP × 3 → ASCT | Primary end point EFS | n = 60 | With median follow-up of 67 mo, median EFS 83 mo and median OS not reached. 5-y OS is 75%. |
| Phase 2 study of RB/RC induction followed by ASCT 2 sites: DFCI and WUSTL Merryman et al14 (2020) | DFCI: 18-69 y, untreated MCL, transplant eligible WUSTL: age 18-65 y, untreated MCL, transplant eligible | DFCI: BR × 3 cycles then R-high-dose cytarabine × 3 cycles → ASCT WUSTL: BR alternating with R-HIDAC, total 6 cycles → ASCT | Primary end point ORR | n = 88 | End-of-induction ORR 97%. After a median follow-up of 33 mo, 3-y PFS 83% and 3-y OS 92%. |
| Phase 2 study of R-HCVAD regimen alternating with high-dose methotrexate and cytarabine Massaro et al16 (2021) Chihara et al15 (2016) | Age <70 y, untreated MCL, transplant eligible | R-HCVAD regimen alternating with high-dose methotrexate and cytarabine × 4 cycles. If CR → no further tx PR → consolidative ASCT | Primary end point complete response rate | n = 63 | With median follow-up of 10.5 years, 10-year PFS and OS of 35% and 61% |
| Study/regimenauthor (ref) . | Key eligibility criteria . | Details of regimen . | Primary end point . | Patients . | Outcomes . |
|---|---|---|---|---|---|
| European Mantle Cell Lymphoma Network (MCL Younger): phase 3 study of R-CHOP vs R-CHOP alternating with R-DHAP → ASCT Hermine et al7 (2016) | Untreated MCL Age 18-65 y, stage II-IV, transplant eligible | Arm 1: R-CHOP × 6 cycles followed by HDT/ASCT Arm 2: R-CHOP alternating with R-DHAP followed by HDT/ASCT | Investigator-assessed TTF | n = 497 | TTF significantly longer in cytarabine group: median 9.1 y (95% CI, 6.3-not reached) vs control group: median 3.9 y (3.2-4.4); HR, 0.56; P = .038. 5-year TTF 65% vs 40%. No OS difference. |
| LYMA phase 3 study of R-DHAP → ASCT → rituximab maintenance vs other Le Gouill et al8 (2017) | Untreated MCL Age >65 y, stages II-IV, transplant eligible | Arm 1: R-DHAP (platinum derivative) × 4 cycles, if CR/PR then HDT/ASCT then rituximab maintenance every 2 mo for 3 y *If <CR/PR, then R-CHOP Arm 2: R-DHAP × 4 cycles, if CR/PR then HDT/ASCT then observation | EFS after ASCT | n = 257 | 4-year EFS was 79% (95% CI, 70-86) in the rituximab group vs 61% (95% CI, 51-70) in the observation group (P = .001) 4-year OS was 89% (95% CI, 81-94) in the rituximab group vs 80% (95% CI, 72-88) in the observation group (P = .04). |
| Second Nordic MCL study (MCL2): phase 2 study of R-maxi-CHOP alternating with R-HIDAC → ASCT Geisler et al10 (2008) Eskelund et al11 (2016) | Untreated MCL Age <66 y, stages II-IV, transplant eligible | R-maxi-CHOP alternating with R-high-dose cytarabine then HDT/ASCT *Pts in CR who converted from PCR-negative to PCR-positive were offered preemptive rituximab 375 mg/m2/wk for 4 weeks to prevent clinical relapse | OS, EFS, and PFS | n = 160 | 6-year OS, EFS, and PFS were 70%, 56%, and 66%, respectively. |
| GELA phase 2 study: R-CHOP × 3 followed by R-DHAP × 3 → ASCT Delarue et al12 (2013) | Untreated MCL Stage III-IV, transplant eligible Blastoid variants excluded | CHOP × 2, R-CHOP × 1, R-DHAP × 3 → ASCT | Primary end point EFS | n = 60 | With median follow-up of 67 mo, median EFS 83 mo and median OS not reached. 5-y OS is 75%. |
| Phase 2 study of RB/RC induction followed by ASCT 2 sites: DFCI and WUSTL Merryman et al14 (2020) | DFCI: 18-69 y, untreated MCL, transplant eligible WUSTL: age 18-65 y, untreated MCL, transplant eligible | DFCI: BR × 3 cycles then R-high-dose cytarabine × 3 cycles → ASCT WUSTL: BR alternating with R-HIDAC, total 6 cycles → ASCT | Primary end point ORR | n = 88 | End-of-induction ORR 97%. After a median follow-up of 33 mo, 3-y PFS 83% and 3-y OS 92%. |
| Phase 2 study of R-HCVAD regimen alternating with high-dose methotrexate and cytarabine Massaro et al16 (2021) Chihara et al15 (2016) | Age <70 y, untreated MCL, transplant eligible | R-HCVAD regimen alternating with high-dose methotrexate and cytarabine × 4 cycles. If CR → no further tx PR → consolidative ASCT | Primary end point complete response rate | n = 63 | With median follow-up of 10.5 years, 10-year PFS and OS of 35% and 61% |
BR, bendamustine-rituximab; EFS, event-free survival; HCT, high-dose chemotherapy; PR, partial response; Pts, patients; RB/RC, rituximab bendamustine/rituximab cytarabine; tx, treatment.