Treatment regimens for multifocal or multisystem adult LCH (series of >10 patients)
| Treatment . | Dose . | Type of study . | n . | Overall response . | Median duration of response (range) . | Progression rate at 3 y (%) . | Comments . | Reference . |
|---|---|---|---|---|---|---|---|---|
| Cladribine | Cladribine 0.14 mg/kg IV d 1-5 (total of 6 cycles; 28 d/cycle) | P | 13 | 75 | 36 mo (1-65+) | ND | Newly diagnosed and relapsed/refractory settings; no patient with CNS, liver, or spleen involvement; 54% grade 3/4 neutropenia; 15% febrile neutropenia; no grade 3/4 anemia or thrombocytopenia | Saven 1999125 |
| Cladribine 5 mg/m2 IV d 1-5 (total of 6 cycles; 28 d/cycle) | R | 22 | 41* | ND | ND | Newly diagnosed and relapsed/refractory settings; all with unifocal or multifocal bone lesions ± other organ involvement; grade 3/4 cytopenias, 22% | Cantu 2012126 | |
| Cladribine 0.14 mg/kg IV d 1-5 (3-6 cycles; 28 d/cycle) | R | 22 | 88 | ND | 35 | Relapsed/refractory setting; 56% nonpituitary CNS, 43% lung, and 13% nodal involvement; 46% CR and 46% PR among those with CNS disease | Néel 2020127 | |
| Cladribine 5 mg/m2 or 0.14 mg/kg IV d 1-5 or (1-9 cycles; 28 d/cycle) | R | 38 | 79 | NR (5y, 70%) | Newly diagnosed and relapsed/refractory settings; 60% lung, 30% lymph nodes, 27% pituitary; 26% CR, 53% PR; responses seen in all disease sites; PFS similar between CR and PR patients; trend toward longer PFS in non-BRAF V600E | Goyal 2021120 | ||
| CEVP | Cyclophosphamide 750 mg/m2 IV day 1; etoposide 100 mg/m2 IV d 1-3; vindesine 4 mg IV d 1; prednisone 100 mg PO d 1-5 (median 5 cycles; 21 d/cycle) | R | 31 | 70 | ND | 20 | Newly diagnosed and relapsed/refractory settings; 48% lung, 19% liver, and 7% spleen involvement; organ-specific responses not reported; any neutropenia, 48%; any thrombocytopenia, 13%; any hepatotoxicity, 23% | Duan 2016128 |
| Cytarabine | 100 mg/m2 IV d 1-5 (6 cycles; 28 d/cycle) | R | 24 | 79* | ND | ND | Newly diagnosed and relapsed/refractory settings; all with unifocal or multifocal bone lesions ± other organ involvement; grade 3/4 cytopenias, 20% | Cantu 2012126 |
| Hydroxyurea | Hydroxyurea 500 mg PO bid | R | 10 | 60 | ND | 40 | Restricted to skin, oral, bone, or lymph node limited disease | Zinn 2016110 |
| MACOP-B | Cyclophosphamide 350 mg/m2 IV + doxorubicin 50 mg/m2 IV d 1, 15, 29, 43, and 71; methotrexate 400 mg/m2 IV d 8, 36, and 64 with leucovorin rescue vincristine 1.4 mg/m2 IV d 8, 22, 36, 50, and 64; bleomycin 10 mg/m2 IV d 22, 50, and 78; prednisone 40 mg/m2 PO d 1-84 | R | 11 | 100 | 47+ months (5-228+) | 30 | Newly diagnosed and relapsed/refractory settings; 36% lung and 9% spleen involvement; organ-specific responses not reported; grade 3 neutropenia, 36%; grade 3 hepatotoxicity, 9%; no febrile neutropenia | Derenzini 2015129 |
| Methotrexate + cytarabine (MC) | Methotrexate 1 g/m2 IV over 24 h day 1 cytarabine 100 mg/m2 IV over 24 h d 1-5 (6 cycles; 35 d/cycle) | P | 83 | 88 | ND | 32 | Newly diagnosed setting; 68% lung, 28% liver, 13% spleen, and 4% nonpituitary CNS involvement; organ-specific responses not reported; 94% grade 3/4 neutropenia; 33% grade 3/4 thrombocytopenia; 48% febrile neutropenia; no treatment related death | Cao 202044 |
| Vinblastine + prednisone (VbP) | Vinblastine 6 mg/m2 (10 mg maximum) IV weekly × 6, followed by maintenance phase dosing every 3 wk × 6-12 mo; prednisone 40 mg/m2 PO daily × 4 wk, then taper, followed by 40 mg/m2 PO maintenance phase dosing d 1-5 every 3 wk × 6-12 mo | R | 19 | 16* | ND | ND | Newly diagnosed and relapsed/refractory settings; all with unifocal or multifocal bone lesions ± other organ involvement; grade 3/4 neuropathy, 75% | Cantu 2012126 |
| R | 35 | 71 | ND | 35 | Newly diagnosed and relapsed/refractory settings; 30% lung, 15% liver, 7% nonpituitary CNS, and 7% nodal involvement; organ-specific responses not reported; grade 3/4 neutropenia, 17%; grade 2 neuropathy, 26% | Tazi 2017116 | ||
| VbPMM | Vinblastine 6 mg/m2 (6 mg maximum) IV d 1; prednisolone 2 mg/kg (60 mg maximum) PO d 1-5; methotrexate 20 mg/m2 PO d 15; 6-mercaptopurine 1.5 mg/kg PO d 1-28 (9 cycles; 28 d/cycle) | R | 13 | 85 | ND | 45 | Newly diagnosed and relapsed/refractory settings; 21% lung, 21% nodal, and 7% nonpituitary CNS involvement; organ-specific responses not reported; grade 3/4 neutropenia, 21%; febrile neutropenia, 7%; grade 3 hepatotoxicity, 7%; grade 5 bleeding, 7% | Morimoto 2013130 |
| Vindesine + prednisone (VP) | Vindesine 4 mg IV d 1; prednisone 100 mg PO d 1-5 (median 5 cycles; 21 d/cycle) | R | 14 | 64 | ND | 40 | Newly diagnosed and relapsed/refractory settings; 50% lung, 7% liver, and 14% spleen involvement; organ-specific responses not reported; any neutropenia, 7%; no thrombocytopenia; any hepatotoxicity, 7% | Duan 2016128 |
| Treatment . | Dose . | Type of study . | n . | Overall response . | Median duration of response (range) . | Progression rate at 3 y (%) . | Comments . | Reference . |
|---|---|---|---|---|---|---|---|---|
| Cladribine | Cladribine 0.14 mg/kg IV d 1-5 (total of 6 cycles; 28 d/cycle) | P | 13 | 75 | 36 mo (1-65+) | ND | Newly diagnosed and relapsed/refractory settings; no patient with CNS, liver, or spleen involvement; 54% grade 3/4 neutropenia; 15% febrile neutropenia; no grade 3/4 anemia or thrombocytopenia | Saven 1999125 |
| Cladribine 5 mg/m2 IV d 1-5 (total of 6 cycles; 28 d/cycle) | R | 22 | 41* | ND | ND | Newly diagnosed and relapsed/refractory settings; all with unifocal or multifocal bone lesions ± other organ involvement; grade 3/4 cytopenias, 22% | Cantu 2012126 | |
| Cladribine 0.14 mg/kg IV d 1-5 (3-6 cycles; 28 d/cycle) | R | 22 | 88 | ND | 35 | Relapsed/refractory setting; 56% nonpituitary CNS, 43% lung, and 13% nodal involvement; 46% CR and 46% PR among those with CNS disease | Néel 2020127 | |
| Cladribine 5 mg/m2 or 0.14 mg/kg IV d 1-5 or (1-9 cycles; 28 d/cycle) | R | 38 | 79 | NR (5y, 70%) | Newly diagnosed and relapsed/refractory settings; 60% lung, 30% lymph nodes, 27% pituitary; 26% CR, 53% PR; responses seen in all disease sites; PFS similar between CR and PR patients; trend toward longer PFS in non-BRAF V600E | Goyal 2021120 | ||
| CEVP | Cyclophosphamide 750 mg/m2 IV day 1; etoposide 100 mg/m2 IV d 1-3; vindesine 4 mg IV d 1; prednisone 100 mg PO d 1-5 (median 5 cycles; 21 d/cycle) | R | 31 | 70 | ND | 20 | Newly diagnosed and relapsed/refractory settings; 48% lung, 19% liver, and 7% spleen involvement; organ-specific responses not reported; any neutropenia, 48%; any thrombocytopenia, 13%; any hepatotoxicity, 23% | Duan 2016128 |
| Cytarabine | 100 mg/m2 IV d 1-5 (6 cycles; 28 d/cycle) | R | 24 | 79* | ND | ND | Newly diagnosed and relapsed/refractory settings; all with unifocal or multifocal bone lesions ± other organ involvement; grade 3/4 cytopenias, 20% | Cantu 2012126 |
| Hydroxyurea | Hydroxyurea 500 mg PO bid | R | 10 | 60 | ND | 40 | Restricted to skin, oral, bone, or lymph node limited disease | Zinn 2016110 |
| MACOP-B | Cyclophosphamide 350 mg/m2 IV + doxorubicin 50 mg/m2 IV d 1, 15, 29, 43, and 71; methotrexate 400 mg/m2 IV d 8, 36, and 64 with leucovorin rescue vincristine 1.4 mg/m2 IV d 8, 22, 36, 50, and 64; bleomycin 10 mg/m2 IV d 22, 50, and 78; prednisone 40 mg/m2 PO d 1-84 | R | 11 | 100 | 47+ months (5-228+) | 30 | Newly diagnosed and relapsed/refractory settings; 36% lung and 9% spleen involvement; organ-specific responses not reported; grade 3 neutropenia, 36%; grade 3 hepatotoxicity, 9%; no febrile neutropenia | Derenzini 2015129 |
| Methotrexate + cytarabine (MC) | Methotrexate 1 g/m2 IV over 24 h day 1 cytarabine 100 mg/m2 IV over 24 h d 1-5 (6 cycles; 35 d/cycle) | P | 83 | 88 | ND | 32 | Newly diagnosed setting; 68% lung, 28% liver, 13% spleen, and 4% nonpituitary CNS involvement; organ-specific responses not reported; 94% grade 3/4 neutropenia; 33% grade 3/4 thrombocytopenia; 48% febrile neutropenia; no treatment related death | Cao 202044 |
| Vinblastine + prednisone (VbP) | Vinblastine 6 mg/m2 (10 mg maximum) IV weekly × 6, followed by maintenance phase dosing every 3 wk × 6-12 mo; prednisone 40 mg/m2 PO daily × 4 wk, then taper, followed by 40 mg/m2 PO maintenance phase dosing d 1-5 every 3 wk × 6-12 mo | R | 19 | 16* | ND | ND | Newly diagnosed and relapsed/refractory settings; all with unifocal or multifocal bone lesions ± other organ involvement; grade 3/4 neuropathy, 75% | Cantu 2012126 |
| R | 35 | 71 | ND | 35 | Newly diagnosed and relapsed/refractory settings; 30% lung, 15% liver, 7% nonpituitary CNS, and 7% nodal involvement; organ-specific responses not reported; grade 3/4 neutropenia, 17%; grade 2 neuropathy, 26% | Tazi 2017116 | ||
| VbPMM | Vinblastine 6 mg/m2 (6 mg maximum) IV d 1; prednisolone 2 mg/kg (60 mg maximum) PO d 1-5; methotrexate 20 mg/m2 PO d 15; 6-mercaptopurine 1.5 mg/kg PO d 1-28 (9 cycles; 28 d/cycle) | R | 13 | 85 | ND | 45 | Newly diagnosed and relapsed/refractory settings; 21% lung, 21% nodal, and 7% nonpituitary CNS involvement; organ-specific responses not reported; grade 3/4 neutropenia, 21%; febrile neutropenia, 7%; grade 3 hepatotoxicity, 7%; grade 5 bleeding, 7% | Morimoto 2013130 |
| Vindesine + prednisone (VP) | Vindesine 4 mg IV d 1; prednisone 100 mg PO d 1-5 (median 5 cycles; 21 d/cycle) | R | 14 | 64 | ND | 40 | Newly diagnosed and relapsed/refractory settings; 50% lung, 7% liver, and 14% spleen involvement; organ-specific responses not reported; any neutropenia, 7%; no thrombocytopenia; any hepatotoxicity, 7% | Duan 2016128 |
CR, complete remission; PR, partial remission; ND, not defined; P, prospective; R, retrospective.
Composite endpoint including patients who did not respond or progressed at 1 y.