Efficacy of select standard and investigational treatments assessed in relapsed/refractory HCL
| . | . | HCL pts. . | . | . | Response rate* . | . | . | Cytopenia†-free survival rate at median follow-up . | ||
|---|---|---|---|---|---|---|---|---|---|---|
| Study type . | Drugs . | Median prior therapies . | Pts. refractory to a purine analog . | OR . | CR . | MRD− . | Time to neutrophils >1500/mm3 (median) . | Time to platelets >10 0000/mm3 (median) . | ||
| Case series10 | Purine analog + rituximab | 26 | 3 | 0% | 96% | 88% | Not reported | Not reported | Not reported | 87% at 78 mos |
| Phase-3 trial14,19 | Moxetumomab pasudotox | 77 | 3 | 49% | 77% | 43% | 35% | ≤4 wks | ≤4 wks | ∼45% at 24.6 mos |
| Phase-2 trials (n = 2)33 | Vemurafenib‡ | 28 | 3 | 21% | 89% | 32% | 0% | 4 wks | 2 wks | 23% at 23 mos |
| 26 | 3 | 4% | 92% | 38% | 0% | ≤4 wks | ≤4 wks | 68% at 12 mos | ||
| Case series (n = 2)31,32 | Low-dose vemurafenib§ | 21 | 3 | Not reported | 100% | 40% | Not reported | 7 wks | 4 wks | ≤50% at 17 mos |
| 27‖ | 3 | Not reported | 100% | 33% | Not reported | Not reported | Not reported | Not reported | ||
| Phase-2 trial35 | Vemurafenib¶ + rituximab | 30 | 3 | 37% | 87% | 87% | 60% | 4 wks | 2 wks | 78% at 37 mos |
| Phase-2 trial74 | Ibrutinib# | 28 | 4 | Not reported | 58% | 23% | ≤11% | 8 wks** | 20 wks | 43% at 42 mos |
| Phase-2 trial88 | Dabrafenib + trametinib†† | 43 | 3 | Not reported | 78% | 49% | 15% | Not reported | Not reported | 78% at 18 mos |
| . | . | HCL pts. . | . | . | Response rate* . | . | . | Cytopenia†-free survival rate at median follow-up . | ||
|---|---|---|---|---|---|---|---|---|---|---|
| Study type . | Drugs . | Median prior therapies . | Pts. refractory to a purine analog . | OR . | CR . | MRD− . | Time to neutrophils >1500/mm3 (median) . | Time to platelets >10 0000/mm3 (median) . | ||
| Case series10 | Purine analog + rituximab | 26 | 3 | 0% | 96% | 88% | Not reported | Not reported | Not reported | 87% at 78 mos |
| Phase-3 trial14,19 | Moxetumomab pasudotox | 77 | 3 | 49% | 77% | 43% | 35% | ≤4 wks | ≤4 wks | ∼45% at 24.6 mos |
| Phase-2 trials (n = 2)33 | Vemurafenib‡ | 28 | 3 | 21% | 89% | 32% | 0% | 4 wks | 2 wks | 23% at 23 mos |
| 26 | 3 | 4% | 92% | 38% | 0% | ≤4 wks | ≤4 wks | 68% at 12 mos | ||
| Case series (n = 2)31,32 | Low-dose vemurafenib§ | 21 | 3 | Not reported | 100% | 40% | Not reported | 7 wks | 4 wks | ≤50% at 17 mos |
| 27‖ | 3 | Not reported | 100% | 33% | Not reported | Not reported | Not reported | Not reported | ||
| Phase-2 trial35 | Vemurafenib¶ + rituximab | 30 | 3 | 37% | 87% | 87% | 60% | 4 wks | 2 wks | 78% at 37 mos |
| Phase-2 trial74 | Ibrutinib# | 28 | 4 | Not reported | 58% | 23% | ≤11% | 8 wks** | 20 wks | 43% at 42 mos |
| Phase-2 trial88 | Dabrafenib + trametinib†† | 43 | 3 | Not reported | 78% | 49% | 15% | Not reported | Not reported | 78% at 18 mos |
OR, overall response; CR, complete response; MRD-neg., negativity for minimal/measurable residual disease.
Among all patients starting study treatment.
Neutrophils <1500/mm3, platelets <10 0000/mm3, or hemoglobin <11 g/dL.
Nine hundred and sixty milligrams twice daily for a median of 16 and 18 weeks in the 2 trials (range 8-20 and 12-24, respectively).
For a median of 3 and 3.8 months in the 2 series (range, 1.9-8.9 and 1.7-19.9 months, respectively), largely at a dose of 240 mg twice daily or 480 mg twice daily.
Three out of 27 patients received dabrafenib plus or minus trametinib (not vemurafenib); 10/27 patients were included also among the 21 patients of the first series and were updated in the second series.
Nine hundred and sixty milligrams twice daily for a total of 8 weeks.
Four hundred and twenty milligrams or 840 mg continuously for an indefinite duration (median not reported; median follow-up, 3.5 years).
Refers to the lower threshold of 1000/mm3 (time to neutrophils >1500/mm3 was not reported).
One hundred and fifty milligrams twice daily (dabrafenib) plus 2 mg die (trametinib) continuously for an indefinite duration (median of 17 months).