Interim Analysis of Phase 2 ICLL01: Ofatumumab and High-Dose Methylprednisolone in Patients at Highest Risk for Relapsed/Refractory CLL
In patients with heavily pretreated, relapsed or refractory CLL, ofatumumab has been shown to result in a 58% ORR (Wierda WG, et al. J Clin Oncol. 2010;28:1749-1755). In addition, high-dose steroids have been shown to be active in patients with CLL who have a poor prognosis or p53 impairment (Castro JE, et al. Leukemia. 2008;22:2048-2053). Thus, the phase 2 ICLL01 trial was undertaken to evaluate the safety and efficacy of bendamustine, ofatumumab, and high-dose methylprednisolone (BOMP) for physically fit patients with relapsed/refractory CLL who had progressed despite receiving 1 to 3 previous treatment regimens. At ASH 2014, de Guibert and colleagues presented a planned interim analysis of this trial (Blood. 2014;124. Abstract 3341).
Among the 55 patients in this interim analysis, the primary end point was the rate of CR after 6 cycles of BOMP, with IWCLL response evaluation performed 3 months after the last cycle. These patients were considered to be in the highest risk category, with a median CIRS comorbidity score of 2 to 6, and 37% of the patients had received 2 to 3 previous therapies, including fludarabine-based combinations in 91% of the cases. Moreover, 90% of the patientsdid not have an IGVH mutation, 39% had complex karyotypes, and 27% and 26% of patients had del17p and del11q, respectively. In addition, 31%, 26%, and 9% of the patients had mutations in TP53, SF3B1, and NOTCH1,respectively.
In the intent-to-treat population, the ORR was 76% (20% CR, 56% PR, and 9% with stable disease). Minimal residual disease in peripheral blood was negative in 29% of cases. Of the responding patients, 5 subsequently underwent allogeneic stem-cell transplantation with a persistent CR. The median OS had not been reached as of this report (estimated as 84% at 18 months), and the median PFS was 17.5 months. The OS and PFS rates were lowest in the highest-risk patients (those with del17p and TP53 mutation). Over a median follow-up of 16.2 months, there were 22 cases of relapse or disease progression recorded, including 4 cases of Richter’s syndrome; 17 of these relapsed patients underwent further treatment with ibrutinib.
Notable grade 3/4 AEs occurred in 78% of the patients, and included neutropenia, thrombocytopenia, anemia, infection, hyperglycemia, and liver enzyme elevation.
The treatment of relapsed or refractory CLL is a challenge, especially after patients receive FCR-based therapies. The researchers concluded that the response and survival results are noteworthy, especially considering that more than 60% of these patients were high risk, and that this protocol may serve as a worthy comparator against emerging therapies for patients with relapsed or refractory high-risk CLL.