Results of a phase II study on panobinostat combined with rituximab in heavily pre-treated DLBCL

On 28 June 2018, Jeffrey A. Barnes from Massachusetts General Hospital Cancer Center, Dana‐Farber Cancer Institute, Boston, MA, USA, and colleagues published an open label phase II clinical trial (NCT01282476) on panobinostat plus rituximab in patients with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) in Hematological Oncology.

The aim of the study was to evaluate the safety and efficacy of panobinostat in combination with rituximab for the treatment of heavily pre-treated DLBCL patients who were ineligible for or relapsed after autologous stem cell transplantation (auto-SCT). The primary endpoint was overall response rate (ORR). Secondary endpoints included progression-free survival (PFS) rate and toxicities.

Patients and methods:

• N = 18 patients
• Median age: 68 years (range, 37–83)
• Median number of prior therapies: 5 (range, 1–11)
• Median days from prior therapies: 117 (range, 10–776)
• Refractory to prior therapy: 14 (78%)
• Prior autologous auto-SCT: 4 (22%)
• Treatment:
  • N = 12 patients received panobinostat (40 mg orally) three times weekly from day 1 to 28; of these, n = 5 patients had treatment related adverse events (AEs) and required dose reduction to an every other week schedule
  • N = 6 patients received panobinostat (40 mg orally) three times every other week
  • Cycle duration: 28 days
  • All patients received rituximab (375 mg/m² IV) on days 1, 8, 15, and 22 of cycle 1, and then on day 1 of cycles 2 to 6
  • Patients without disease progression after 6 cycles continued panobinostat monotherapy for up to 6 additional cycles in the absence of disease progression

Key findings:

• Efficacy
  • ORR: 11% (90% CI, 2–34); two patients had a partial response
  • The duration of response: 51 and 60 days
  • Five additional subjects had stable disease with 3 subjects having tumor reduction between 27 and 44%
  • One subject with stable disease remained on therapy a total of 12 cycles
  • Median PFS: 54.5 days
  • 6-month PFS: 6% (90% CI, 0.7–21)
• Safety
  • The most common toxicities: thrombocytopenia (78%), fatigue (61%), anemia (56%), diarrhea (44%), nausea (28%), lymphopenia (28%), anorexia (28%), and hypophosphatemia (28%)
  • N =15 patients discontinued treatment due to progressive disease, n = 1 patient was removed from study consent, n = 1 patient completed all 12 treatment cycles, and n = 1 patient discontinued treatment due to recurrent thrombocytopenia

These findings showed that panobinostat plus rituximab is “well-tolerated and can induce responses in a minority of heavily pre-treated patients with DLBCL.” The inferior ORR shows an unmet need to find the population which most likely reach response to histone deactylase inhibitors.