Mogamulizumab is an effective treatment option for relapsed/refractory cutaneous T-cell lymphoma (CTCL), according to researchers.
In the phase 3 MAVORIC trial, mogamulizumab prolonged progression-free survival (PFS) and produced better overall response rates (ORRs) than vorinostat in patients with relapsed/refractory CTCL.
The most common adverse events (AEs) in patients treated with mogamulizumab were infusion-related reactions, diarrhea, fatigue, and drug eruptions.
Youn Kim MD, of the Stanford Cancer Institute in Palo Alto, California, and her colleagues reported these results in The Lancet Oncology.
The results supported the recent approval of mogamulizumab by the US Food and Drug Administration.
The study was sponsored by Kyowa Hakko Kirin Co., Ltd., the company developing/marketing mogamulizumab.
For MAVORIC, researchers compared mogamulizumab and vorinostat in adults with mycosis fungoides (MF) or Sézary syndrome (SS) who had received at least 1 prior systemic therapy.
The trial included 372 patients who were randomized to receive mogamulizumab at 1.0 mg/kg (weekly for the first cycle and then every 2 weeks) or vorinostat at 400 mg daily for 28-day cycles.
Patients were treated until disease progression or unacceptable toxicity. Patients on vorinostat who progressed or experienced intolerable toxicity after 2 cycles, despite dose reduction and appropriate management of AEs, could cross over to treatment with mogamulizumab.
There were 184 patients in the mogamulizumab arm and 186 in the vorinostat arm who received treatment.
The median duration of follow-up was 17.0 months.
Most patients (n=157) ultimately discontinued mogamulizumab. Reasons included:
- Disease progression (n=76 by CTCL criteria and 22 by clinical criteria)
- AEs (n=28)
- Withdrawn consent (n=13)
- Investigator decision (n=9)
- Patient decision (n=6)
- Death (n=2)
- Noncompliance (n=1).
Most patients (n=136) in the vorinostat arm crossed over to the mogamulizumab arm, 109 due to disease progression and 27 due to treatment intolerance.
Of the 40 patients who did not cross over to mogamulizumab, reasons for stopping vorinostat included:
- Progressive disease (n=10 by CTCL criteria and 8 by clinical criteria)
- Patient decision (n=9)
- Withdrawn consent (n=5)
- AEs (n=5)
- Death (n=2)
- Lost to follow-up (n=1).
At the data cutoff, there were 27 patients assigned to mogamulizumab and 10 assigned to vorinostat who remained on treatment. There were 31 patients still on treatment who had crossed over from vorinostat to mogamulizumab.
Baseline characteristics were similar between the treatment arms.
|Median age||64 (range, 54-73)||65 (range, 56-72)|
|Male||109 (59%)||107 (58%)|
|Female||77 (41%)||79 (42%)|
|MF||105 (56%)||99 (53%)|
|SS||81 (44%)||87 (47%)|
|Time from diagnosis, months||41.0|
|Median number of previous systemic regimens||3 (range, 2-5)||3 (range, 2-5)|
PFS and ORR
Mogamulizumab provided a significant improvement in PFS, the study’s primary endpoint.
According to investigators, the median PFS was 7.7 months with mogamulizumab and 3.1 months with vorinostat (hazard ratio=0.53, P<0.0001).
According to independent review, the median PFS was 6.7 months and 3.8 months, respectively (hazard ratio=0.64, P<0.0007).
There was a significant improvement in ORR with mogamulizumab.
According to independent review, the global ORR was 23% (43/186) in the mogamulizumab arm and 4% (7/186) in the vorinostat arm (risk ratio=19.4, P<0.0001).
According to investigators, the global ORR was 28% (52/186) and 5% (9/186), respectively (risk ratio=23.1, P<0.0001).
For patients with MF, the investigator-assessed ORR was 21% (22/105) with mogamulizumab and 7% (7/99) with vorinostat.
For SS patients, the investigator-assessed ORR was 37% (30/81) and 2% (2/87), respectively.
Responses by disease compartment were superior with mogamulizumab as well.
The investigator-assessed blood ORR was 68% (83/122) with mogamulizumab and 19% (23/123) with vorinostat. The skin ORR was 42% (78/186) and 16% (29/186), respectively.
The lymph node ORR was 17% (21/124) and 4% (5/122), respectively. The viscera ORR was 0% in both arms.
Among patients who crossed over from vorinostat to mogamulizumab, the ORR was 31% (41/133). In these patients, the median PFS was 8.9 months.
In the 319 patients who were assigned to mogamulizumab or crossed over to that arm, the median PFS was 8.4 months.
The most common treatment-emergent, grade 1-2 AEs, occurring in at least 20% of patients in either arm (mogamulizumab and vorinostat, respectively), were:
- Thrombocytopenia (14% vs 34%)
- Diarrhea (23% vs 57%)
- Nausea (15% vs 41%)
- Fatigue (22% vs 32%)
- Increased blood creatinine (3% vs 28%)
- Decreased appetite (7% vs 24%)
- Dysgeusia (3% vs 28%)
- Drug eruptions (20% vs 1%)
- Infusion-related reactions (32% vs 1%).
Grade 3 AEs in the mogamulizumab arm included drug eruptions (n=8), hypertension (n=8), pneumonia (n=6), fatigue (n=3), cellulitis (n=3), infusion-related reactions (n=3), sepsis (n=2), decreased appetite (n=2), AST increase (n=2), weight decrease (n=1), pyrexia (n=1), constipation (n=1), nausea (n=1), and diarrhea (n=1).
Grade 4 AEs with mogamulizumab were cellulitis (n=1) and pneumonia (n=1). Grade 5 AEs included pneumonia (n=1) and sepsis (n=1).