Durable Responses in Patients Treated with Galiximab (Anti‑CD80) in Combination with Rituximab for Relapsed or Refractory Follicular Lymphoma: Long-Term Follow-up of a Phase II Clinical Trial

Galiximab is an anti-CD80 monoclonal antibody with human IgG1 constant regions and macaque variable regions. CD80 is an immune costimulatory molecule that is constitutively expressed on the surface of follicular lymphomas. Modest single-agent clinical activity (ORR 11%) was demonstrated in a single agent Phase I study of galiximab in relapsed/refractory, follicular NHL with the observation of late and prolonged responses. We previously conducted a phase II multicenter study evaluating the combination of galiximab and rituximab for relapsed/refractory follicular NHL, and demonstrated an ORR of 64% (17% CR, 14% CRu, and 33% PR). Here, we analyze long-term safety and efficacy data from this trial.  Patients received galiximab (500 mg/m² qwk x 4 weeks) concurrently with a standard course of rituximab (375 mg/m² qwk x 4 weeks).   No maintenance therapy was allowed.  Sixty‑four patients received treatment. Mean age at study entry was 59 yrs. The majority of patients (88%) were Stage III/IV, and FLIPI risk groups were distributed as low (27%), intermediate (39%), and high (34%). All patients had received at least 1 prior lymphoma therapy; 42% were rituximab naïve; rituximab‑refractory patients (no response or a response with TTP<6 months) were excluded.   The median follow-up of responding patients is 45 months (range 9-59 months).  The median PFS was 12.2 months.  20% of patients had PFS durations exceeding 2 years.  37% of patients did not require any additional lymphoma therapy for at least 2 years following treatment (TTNT); 28% had a TTNT of more than 3 years.  Grade, tumor bulk, age, stage, prior rituximab exposure, and FLIPI score did not predict for PFS duration of > 2 years, or TTNT duration of > 2 years (p=NS, chi-square analysis).  Obtaining a CR predicted for PFS and TTNT duration >2 years (p=0.001).  Response duration to prior therapy was not correlated to outcome following rituximab/galiximab therapy (p=0.18).  Quantitative immunoglobulin levels (IgA, IgM and IgG) did not differ between prolonged responders and other patients, and did not significantly change over the first year of follow-up.  Median Cmax, half-life, AUC and Cl were similar between prolonged responders and other patients.  No late opportunistic infections, secondary malignancies, or infusion-associated deaths have been reported.  We conclude that the combination of rituximab and galiximab is well-tolerated in long-term follow-up, with a substantial number of durable responses.  Almost one-third of patients treated with only 4 weeks of this combination do not require additional lymphoma therapy for more than three years.  There is no clear prognostic marker that predicts for prolonged benefit from the combination.  These durable responses provide strong rationale for ongoing phase III clinical trials of the galiximab/rituximab combination.