Regimens in ATL
| Study/year . | Regimen . | Evaluable patients, n . | ORR, % . | Survival . | Notes . |
|---|---|---|---|---|---|
| Marçais et al40 /2020 | Retrospective arsenic trioxide with ZDV/ IFN consolidation following induction with chemotherapy or ZDV/IFN | 9 | Median OS 28 mo from start of consolidation (range, 1-70 mo) | As2O3 administered for median 6 mo (2-24 mo) | |
| Phillips et al41 /2019 | Randomized phase 2 mogamulizumab vs investigator’s choice of chemotherapy Relapsed/refractory | 71 | 0 15, investigator assessment | N/A | 96% positive for CCR4, most benefit in leukemic ATL |
| Sharma et al42 /2017 | Phase 2 alemtuzumab Relapsed/refractory | 29 | 52 | 6 mo | Most benefit seen in leukemic disease, all patients reactivated CMV |
| Ishida et al43 /2016 | Multicenter phase 2, lenalidomide Relapsed/refractory | 26 | 42 | OS, 20.3 mo; PFS, 4 mo | Surprisingly long OS given short PFS; possibly more indolent relapses |
| Ratner et al44 /2015 | Phase 1/2 EPOCH with bortezomib and raltegravir front line | 18 | 67 | 6.2 mo | No increased benefit with addition of bortezomib or raltegravir |
| Ishitsuka et al45 /2015 | Phase 2 bortezomib Relapsed/refractory | 15 | 7 | N/A | Study terminated due to lack of efficacy |
| Ishida et al31,32 /2015; update 2019 | Randomized phase 2 VCAP/AMP/VECP ± mogamulizumab front line | 54 | 86 (+moga) 75 (−moga) | 3-y OS, 45% (+moga arm) vs 50% (−moga) | Improved CR rate with moga (52% vs 33%) No increased PFS/OS, increased risk GVHD Study led to Japanese approval |
| Ishida et al19 /2012 | Multicenter phase 2 mogamulizumab in relapsed refractory | 28 | 50 | 14 mo | Study led to Japanese approval in relapsed refractory disease |
| Ceesay et al 46 /2012 | Phase 2 study CHOP + anti-CD25 monoclonal front line | 15 | 60 | 10 mo | No benefit to addition of anti-CD25 |
| Bazarbachi et al20 /2010 | Meta-analysis ZDV/IFN in aggressive ATL | 254 (n = 75 frontline) | 66 | (5 y) 23% | Retrospective, lymphoma patients better outcomes with chemotherapy Acute and chronic leukemics benefit most from ZDV/IFN p53 mutations resistant |
| Hodson et al47 /2011 | Retrospective study ZDV/IFN at any point for acute or lymphoma | 73 | HR, 0.23 reduced risk of death | Retrospective | |
| Ratner et al; AIDS Malignancy Consortium48 / 2009 | Phase 2 EPOCH followed by ZDV/IFN Front line | 19 | 58 | mPFS and mOS 6 mo | Prospective phase 2 study ZDV/IFN maintenance did not add to survival |
| Kchour et al49 /2009 | Phase 2 ZDV/IFN/ As2O3 newly diagnosed symptomatic chronic ATL | 10 | 100 (7 CR, 2 vgPR,* 1 PR) | 30 d arsenic combined with ZDV/IFN followed by ZDV/IFN. Median study follow up 8 mo (range, 2-15 mo), all patients alive, none progressed. | |
| Tsukasaki et al29 /2007 | Randomized phase 3 VCAP/AMP/VECP vs CHOP14 front line | 118 | 72 66 | (3 y) 24% 13% | More toxicities, only 32% completed planned treatment |
| Hermine et al50 /2004 | Phase 2 IFN/arsenic trioxide Relapsed/refractory | 7 | 7.5 mo | Treatment discontinued after median 22 d due to toxicity (n = 3) or progression (n = 4) |
| Study/year . | Regimen . | Evaluable patients, n . | ORR, % . | Survival . | Notes . |
|---|---|---|---|---|---|
| Marçais et al40 /2020 | Retrospective arsenic trioxide with ZDV/ IFN consolidation following induction with chemotherapy or ZDV/IFN | 9 | Median OS 28 mo from start of consolidation (range, 1-70 mo) | As2O3 administered for median 6 mo (2-24 mo) | |
| Phillips et al41 /2019 | Randomized phase 2 mogamulizumab vs investigator’s choice of chemotherapy Relapsed/refractory | 71 | 0 15, investigator assessment | N/A | 96% positive for CCR4, most benefit in leukemic ATL |
| Sharma et al42 /2017 | Phase 2 alemtuzumab Relapsed/refractory | 29 | 52 | 6 mo | Most benefit seen in leukemic disease, all patients reactivated CMV |
| Ishida et al43 /2016 | Multicenter phase 2, lenalidomide Relapsed/refractory | 26 | 42 | OS, 20.3 mo; PFS, 4 mo | Surprisingly long OS given short PFS; possibly more indolent relapses |
| Ratner et al44 /2015 | Phase 1/2 EPOCH with bortezomib and raltegravir front line | 18 | 67 | 6.2 mo | No increased benefit with addition of bortezomib or raltegravir |
| Ishitsuka et al45 /2015 | Phase 2 bortezomib Relapsed/refractory | 15 | 7 | N/A | Study terminated due to lack of efficacy |
| Ishida et al31,32 /2015; update 2019 | Randomized phase 2 VCAP/AMP/VECP ± mogamulizumab front line | 54 | 86 (+moga) 75 (−moga) | 3-y OS, 45% (+moga arm) vs 50% (−moga) | Improved CR rate with moga (52% vs 33%) No increased PFS/OS, increased risk GVHD Study led to Japanese approval |
| Ishida et al19 /2012 | Multicenter phase 2 mogamulizumab in relapsed refractory | 28 | 50 | 14 mo | Study led to Japanese approval in relapsed refractory disease |
| Ceesay et al 46 /2012 | Phase 2 study CHOP + anti-CD25 monoclonal front line | 15 | 60 | 10 mo | No benefit to addition of anti-CD25 |
| Bazarbachi et al20 /2010 | Meta-analysis ZDV/IFN in aggressive ATL | 254 (n = 75 frontline) | 66 | (5 y) 23% | Retrospective, lymphoma patients better outcomes with chemotherapy Acute and chronic leukemics benefit most from ZDV/IFN p53 mutations resistant |
| Hodson et al47 /2011 | Retrospective study ZDV/IFN at any point for acute or lymphoma | 73 | HR, 0.23 reduced risk of death | Retrospective | |
| Ratner et al; AIDS Malignancy Consortium48 / 2009 | Phase 2 EPOCH followed by ZDV/IFN Front line | 19 | 58 | mPFS and mOS 6 mo | Prospective phase 2 study ZDV/IFN maintenance did not add to survival |
| Kchour et al49 /2009 | Phase 2 ZDV/IFN/ As2O3 newly diagnosed symptomatic chronic ATL | 10 | 100 (7 CR, 2 vgPR,* 1 PR) | 30 d arsenic combined with ZDV/IFN followed by ZDV/IFN. Median study follow up 8 mo (range, 2-15 mo), all patients alive, none progressed. | |
| Tsukasaki et al29 /2007 | Randomized phase 3 VCAP/AMP/VECP vs CHOP14 front line | 118 | 72 66 | (3 y) 24% 13% | More toxicities, only 32% completed planned treatment |
| Hermine et al50 /2004 | Phase 2 IFN/arsenic trioxide Relapsed/refractory | 7 | 7.5 mo | Treatment discontinued after median 22 d due to toxicity (n = 3) or progression (n = 4) |
CMV, cytomegalovirus; mOS, median OS; mPFS, median PFS; N/A, not applicable; ORR, overall response rate; PR, partial response.
vgPR indicates very good partial response, defined as normalization of the complete blood count, and disappearance of all measurable tumors for at least 1 month, but persistence of >5% atypical lymphocytes on the peripheral blood smear.