Italian real life experience with ibrutinib: results of a large observational study on 77 relapsed/refractory mantle cell lymphoma

Abstract

Although sometimes presenting as an indolent lymphoma, mantle cell lymphoma (MCL) is an aggressive disease, hardly curable with standard chemo-immunotherapy. Current approaches have greatly improved patients’ outcomes, nevertheless the disease is still characterized by high relapse rates. Before approval by EMA, Italian patients with relapsed/refractory MCL were granted ibrutinib early access through a Named Patient Program (NPP).An observational, retrospective, multicenter study was conducted. Seventy-seven heavily pretreated patients were enrolled. At the end of therapy there were 14 complete responses and 14 partial responses, leading to an overall response rate of 36.4%. At 40 months overall survival was 37.8% and progression free survival was 30%; disease free survival was 78.6% at 4 years: 11/14 patients are in continuous complete response with a median of 36 months of follow up. Hematological toxicities were manageable, and main extra-hematological toxicities were diarrhea (9.4%) and lung infections (9.0%). Overall, 4 (5.2%) atrial fibrillations and 3 (3.9%) hemorrhagic syndromes occurred.In conclusions, thrombocytopenia, diarrhea and lung infections are the relevant adverse events to be clinically focused on; regarding effectiveness, ibrutinib is confirmed to be a valid option for refractory/relapsed MCL also in a clinical setting mimicking the real world.

Treatment patterns and outcomes among mantle cell lymphoma patients treated with ibrutinib in the United States: a retrospective electronic medical record database and chart review study

“…followed 111 patients with MCL treated with single‐agent ibrutinib 560 mg daily, the median age of patients was 68 years, the median duration on ibrutinib was 8·3 months and the median OS was 22·5 months (95% CI 13·7–NR) 10 . In other retrospective, observational studies, a median OS of 16 months and 22 months were reported by Broccoli et al 2 . and Epperla et al 16 .…”

“…MCL is usually diagnosed as a late‐stage disease that often involves the gastrointestinal tract and bone marrow 1 . Although front‐line therapy can achieve disease control, relapses are expected and most patients will die from their disease 2 . In the USA, there were approximately 70 800 new cases of NHL in 2014, with patients with MCL representing 3–6% of all new cases 3 .…”

Mantle cell lymphoma treatment options for elderly/unfit patients: A systematic review

“…Following removal of duplicate papers, 901 papers remained; of these 805 articles were removed after the titles and abstracts were screened, leaving 66 articles for full screening. From these papers, 16 articles met all the inclusion criteria, and were taken forward for qualitative synthesis ( Table 2 [ 13 , 23 , 24 , 32 , 54 , 55 , 56 , 57 , 58 , 59 – 61 , 63 , 64 , 65 , 67 ]).…”

“…Our study identified five different treatment regimens which had been examined within the criteria of this review: elderly/unfit patients after the introduction of ibrutinib in 2012. The three most frequently studied treatments were R‐CHOP (eight studies [ 13 , 23 , 33 , 55 , 56 , 60 , 61 , 65 ]), ibrutinib (five studies [ 24 , 54 , 59 , 63 ]) and bendamustine (three studies [ 13 , 33 , 60 ]). We found that treatment outcomes in patients treated with R‐CHOP were not inferior to those with ibrutinib or BR.…”

IBRORS-MCL study: a Spanish retrospective and observational study of relapsed/refractory mantle-cell lymphoma treated with ibrutinib in routine clinical practice

“…Our series mainly included MCL patients with advanced disease, with more than one extranodal site affected, who had been moderately pre-treated (77% of patients had received 1–2 prior lines of therapy) compared with the patients receiving 2 prior lines of therapy or less in phase II SPARK (52.5%) and phase III RAY (68%) studies [ 8 , 9 ] and other real-world cohorts including more heavily pre-treated patients (ranging from 55 to 70%) [ 11 , 13 , 15 ].…”