Combining Imbruvica (ibrutinib) with Revlimid (lenalidomide) and Rituxan (rituximab) may improve the poor outcomes of relapsed mantle cell lymphoma patients with certain genetic alterations, a Phase 2 trial suggests.
But the combination, researchers said, was no better than Imbruvica, or Imbruvica plus Rituxan, among patients without the specific mutations in the TP53 gene or combined deletions of TP53 and CDKN2A genes.
The study, “Ibrutinib, lenalidomide, and rituximab in relapsed or refractory mantle cell lymphoma (PHILEMON): a multicentre, open-label, single-arm, phase 2 trial,” was published in the journal The Lancet Haematology.
In prior Phase 2 and Phase 3 trials for mantle cell lymphoma patients, Imbruvica has shown promising activity, with 65 to 75 percent of patients achieving a confirmed response. The therapy also showed a good tolerability profile.
Similarly, a combination of the immunomodulator Revlimid and Rituxan has also been shown to be very active in mantle cell lymphoma, either as a first-line therapy or after relapse.
That led researchers to hypothesize that “the combination of all three drugs would improve efficacy compared with previously published data on either regimen alone,” according to the study.
Researchers began a clinical trial (NCT02460276), currently ongoing, with 50 relapsed or refractory mantle cell lymphoma patients from 10 centers in Sweden, Finland, Norway, and Denmark. Participants had been previously treated with at least one Rituxan-containing regimen.
Patients received the combination for 12 cycles, lasting 28 days each (induction phase), followed by a maintenance phase with Imbruvica and Rituxan for 56 days. Treatment was given until a patient’s disease progressed or they experienced unacceptable toxicity.
During the induction phase, patients received intravenous or subcutaneous Rituxan once a week during the first cycle, followed by once every eight weeks. An oral tablet of Imbruvica was given every day and Revlimid was given orally once a day for the first 21 days of every cycle.
The trial’s primary goal is to assess the proportion of patients who achieve either a partial or a complete response to the treatment. The number of patients who achieved molecular remission — a complete remission with no evidence of disease in the bone marrow — was also assessed.
Additionally, researchers assessed the therapy’s activity in patients with mutations associated with poor outcomes, such as those in the TP53 gene.
After a median follow-up of 1.5 years, 76 percent of patients had responded to the treatment. Fifty-six percent were complete responses, meaning all signs of the cancer had disappeared.
Patients lived for a median of 22 months, and remained without signs of disease progression for 16 months.
The findings showed that the triple combination is better than a combination of Imbruvica and Rituxan or Imbruvica alone in these patients, and researchers say that the treatment induced higher rates of complete and molecular responses.
Patients with TP53 mutations had similar responses to the treatment, compared to those without these genetic traits. This suggests that the treatment had a similarly high activity in patient groups.
“Even with intensive immunochemotherapy and autologous stem-cell transplantation, the response to treatment and eventual outcome were poor for patients with TP53 mutations,” researchers explained, suggesting that a combination of Imbruvica, Revlimid and Rituxan may overcome the poor prognosis of patients with these genetic alterations.
Overall, the study showed that the combination is active in patients with relapsed or refractory mantle cell lymphoma, leading to high response rates. But the treatment might only improve the outcomes of those with certain genetic mutations.