Page 150 - 2019_05-HaematologicaMondo-web

Adrienne A. Phillips et al.
Figure 1. CONSORT diagram. ITT: intent-to-treat.
the 18 patients crossed over to mogamulizumab, three (17%) demonstrated a response.
Responses to mogamulizumab were seen in all enrolled subtypes. Best and confirmed responses by ATL subtype to mogamulizumab were chronic 71% (5/7) and 43% (3/7); lymphoma 32% (6/19) and 5% /1/19); and acute 24% (5/21) and 5% (1/21), respectively. In the moga- mulizumab arm, four out of the seven chronic patients had unfavorable characteristics; of those three had a response. Of the three patients with favorable characteris- tics, two had a response. Three chronic patients initially received Investigator’s Choice regimen. All three crossed over to treatment with mogamulizumab; there were no responses to either treatment in these patients.
In the mogamulizumab arm, best response was 46% (13/28) for patients with ECOG 0/1 and 16% (3/19) for ECOG 2. In the Investigator’s Choice group, no responses were observed.
Median time to response in the mogamulizumab arm was 1.13 (95%CI: 0.87-3.40) months, with most (75%) responses occurring by the first assessment at 4 weeks. Median DoR in the mogamulizumab arm was 5.65 (95%CI: 3.63-not reached) months.
Median PFS was 0.93 (95%CI: 0.87-1.13) and 0.88 (95%CI: 0.50-0.93) months in the mogamulizumab and investigator’s choice arms, respectively. The observed hazard ratio (HR) for PFS was 0.71 (95%CI: 0.41-1.21) (Figure 2). As PFS may have been affected by imbalances in baseline prognostic characteristics, post hoc sensitivity analyses adjusting for these imbalances were performed (Figure 3). Adjusting for the imbalances in ECOG perform- ance status and for response to last prior ATL therapy yielded an HR for PFS of 0.57 (95%CI: 0.327-0.983) and
0.58 (95%CI: 0.330-1.006), respectively. Survival analysis was confounded by the one-way crossover design; how- ever, there was no apparent overall survival advantage or disadvantage associated with mogamulizumab use (Online Supplementary Figure S1).
Five patients (1 acute, 2 lymphoma, and 2 chronic) pro- gressed per protocol in a single compartment but derived clinical benefit according to Investigator Assessment. These patients were allowed to continue treatment after discussion with the study sponsor (Figure 4 and Online Supplementary Figure S2). These patients remained on mogamulizumab with clinical improvement and/or dis- ease control for a median of 230 (range, 182-463) days. Four of the five patients had blood disease, and response continued through to the end of data collection for this group. Of these four patients, one is alive 56 months post initial treatment with subsequent spot radiation to 3 skin lesions. Another subject is alive 41 months post initial treatment and progressed in lymph nodes per size criteria; however, the investigator felt these were more likely to be reactive nodes. Two patients progressed in skin and an additional patient in skin and nodes. No subjects directly bridged to transplant without subsequent therapy in either arm of the study (Figure 4).
Safety
Mean (±Standard Deviation) duration of randomized treatment (78.0±141.51 vs. 26.5±33.61 days) and the num- ber of treatment cycles initiated (3.1±4.60 vs. 1.5±0.98) were higher in the mogamulizumab arm than the investi- gator’s choice arm.
The overall incidence of treatment-related any-grade (83% vs. 88%), grade ≥3 (32% vs. 29%), or serious (23%
996
haematologica | 2019; 104(5)