Prospective subgroup analyses of the randomized MCL‐002 (SPRINT) study: lenalidomide versus investigator's choice in relapsed or refractory mantle cell lymphoma

Abstract

SummaryIn the mantle cell lymphoma (MCL)‐002 study, lenalidomide demonstrated significantly improved median progression‐free survival (PFS) compared with investigator's choice (IC) in patients with relapsed/refractory MCL. Here we present the long‐term follow‐up data and results of preplanned subgroup exploratory analyses from MCL‐002 to evaluate the potential impact of demographic factors, baseline clinical characteristics and prior therapies on PFS. In MCL‐002, patients with relapsed/refractory MCL were randomized 2:1 to receive lenalidomide (25 mg/day orally on days 1–21; 28‐day cycles) or single‐agent IC therapy (rituximab, gemcitabine, fludarabine, chlorambucil or cytarabine). The intent‐to‐treat population comprised 254 patients (lenalidomide, n = 170; IC, n = 84). Subgroup analyses of PFS favoured lenalidomide over IC across most characteristics, including risk factors, such as high MCL International Prognostic Index score, age ≥65 years, high lactate dehydrogenase (LDH), stage III/IV disease, high tumour burden, and refractoriness to last prior therapy. By multivariate Cox regression analysis, factors associated with significantly longer PFS (other than lenalidomide treatment) included normal LDH levels (P < 0·001), nonbulky disease (P = 0·045), <3 prior antilymphoma treatments (P = 0·005), and ≥6 months since last prior treatment (P = 0·032). Overall, lenalidomide improved PFS versus single‐agent IC therapy in patients with relapsed/refractory MCL, irrespective of many demographic factors, disease characteristics and prior treatment history.

Final Results of a Phase I/II Trial of the Combination Bendamustine and Rituximab With Temsirolimus (BeRT) in Relapsed Mantle Cell Lymphoma and Follicular Lymphoma

“…Especially in MCL several novel agents have been successfully introduced, particularly BTK-inhibitors have significantly changed the current treatment and trial strategies. [23][24][25] In parallel, other drugs have been successfully tested, for example, Temsirolimus, Lenalidomid or Bortezomib and recently Venetoclax, [26][27][28][29][30][31] however, their optimal placement within treatment sequencing is less clear. In FL Idelalisib, a PI3K inhibitor, has been approved and other agents of this class are on their way to clinical practice.…”

Cost-effectiveness for KTE-X19 CAR T therapy for adult patients with relapsed/refractory mantle cell lymphoma in the United States

“…The US population's incidence of MCL has increased from 0.80 persons per 100,000 per year in 1995-1999 to 1.15 persons per 100,000 per year in 2009-2013 [4]. Most patients with MCL relapse after first-line therapy (chemo-immunotherapy with/without autologous stem cell transplant) [5]. Subsequently, these patients experience reduced survival, with a median progression free survival (PFS) on standard of care (SoC) following relapse of less than 2 years [6][7][8][9][10].…”

Acalabrutinib for mantle cell lymphoma

“…Patients who relapse are typically treated with salvage chemoimmunotherapy or other approved agents. These include the proteasome inhibitor bortezomib, 13,14 the immunomodulatory agent lenalidomide, [15][16][17][18][19] the mammalian target of rapamycin complex 1 inhibitor temsirolimus (Europe, not United States), [20][21][22][23][24] and the Bruton tyrosine kinase (BTK) inhibitors discussed in the next section. [25][26][27][28][29] The bcl-2 inhibitor venetoclax has orphan drug designation (but not approval) for MCL.…”