CTCL

SOHO 2018 Virtual Coverage | New approaches to the management of CTCL

On September 12–15 2018, the sixth annual meeting of the Society of Hematologic Oncology (SOHO) was held in Houston, Texas. The meeting covered a variety of topics in the latest advances in the pathophysiology and treatment of hematological malignancies.

A presentation by Pierluigi Porcu, Director of Hematological Malignancies at the Sidney Kimmel Cancer Center at Jefferson Health, on new approaches to the management of cutaneous T-cell lymphoma (CTCL) was held on Friday 14 September in the non-Hodgkin lymphoma session.

Dr Porcu first described the outcomes of the MAVORIC phase III study evaluating the efficacy and safety of the anti-CCR4 antibody mogamulizumab vs standard of care vorinostat in patients with relapsed/refractory (R/R) CTCL. The primary endpoint of the study was progression-free survival (PFS). The secondary endpoints were overall response rate (ORR), duration of response (DOR) and improvements in quality of life (QoL) measures. N = 372 patients were enrolled and randomized 1:1 to receive either mogamulizumab 1.0mg/kg weekly in cycle 1 and then bi-weekly in subsequent cycles or vorinostat 400mg orally once daily. MAVORIC is the largest randomized clinical trial in CTCL ever conducted and included 168 patients with Sezary Syndrome, one of the rarest and most aggressive forms of CTCL.

The median PFS for mogamulizumab was 7.7 months (95% CI, 5.67, 10.33) vs vorinostat 3.1 months (95% CI, 2.87, 4.07). The ORR for mogamulizumab was 28.0% and 4.8% for vorinostat (P < 0.0001). The rate of treatment-emergent adverse events (TEAEs) grade ≥3 for mogamulizumab was 42% with 3 patient deaths and 46% for vorinostat with 9 patient deaths. Dr Porcu noted that – as expected - there was a higher frequency of diarrhea, fatigue, nausea, thrombocytopenia, anorexia, dysgeusia and increased Scr for the vorinostat cohort.

Dr Porcu concluded that there were significant improvements in PFS and ORR for the mogamulizumab group compared with vorinostat in patients with R/R CTCL. The results of the quality of life in CTCL patients treated with mogamulizumab vs vorinostat will be presented at the EORTC 2018 meeting in St. Gallen, 27–29 September.

The final study that Dr Porcu presented was the extended follow-up from the ALCANZA phase III trial of brentuximab vedotin vs methotrexate or bexarotene for previously treated CD30+ CTCL. Patients with R/R CD30+ MF or pcALCL were randomized to receive brentuximab vedotin 1.8 mg/kg IV every 3 weeks (n = 64) or physician’s choice of either methotrexate 5-50mg orally weekly or bexarotene 300 mg/m2 orally daily (n = 64). The primary endpoint was ORR lasting ≥4 months. Secondary endpoints included complete response CR, PFS, QoL and peripheral neuropathy.

At a median follow-up of 33.9 months, the ORR4 was significantly increased (60.9%) in brentuximab vedotin vs 7.8% in the investigator’s choice cohort (P < 0.001). The ORR for brentuximab vedotin was 68.8% vs 21.9% investigator’s choice (P < 0.001).

The median PFS was significantly longer with brentuximab vedotin vs physician’s choice (, 15.8 months vs  3.6 months, respectively (HR 0.373, (95% CI, 0.245–0.569) (P < 0.001). Dr Porcu noted that the incidence of peripheral neuropathy was higher in the brentuximab cohort (67%) vs physician’s choice (6%).

Dr Porcu concluded that the extended follow up proved the superiority of brentuximab vedotin to the current standards of care (methotrexate and bexarotene). He highlighted that there are many other new agents currently in phase I­-II trials for the treatment of CTCL, NCT02593045, NCT02580552, NCT02663518, NCT03063632, NCT02783625.

References

Porcu P, New Approaches to the Management of CTCL, 2018 SOHO annual meeting, slides were provided to the Lymphoma Hub by Pierluigi Porcu

Kim YH, et al. Blood 2017 130:817

Horwitz SM, et al. ASH 2017. Abstract 1509

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