First-line response-adapted therapy with rituximab and bendamustine is efficient and well tolerated in patients with MALT Lymphoma – long-term results of the phase II GELTAMO MALT 2008-01 trial

On 11^th August, in a Letter to the Editor of the journal Blood, Antonio Salar, MD, from Hospital del Mar, Barcelona, Spain, and colleagues reported results of a multicenter, prospective, non-randomized phase II trial assessing bendamustine plus rituximab for newly diagnosed patients with extranodal Mucosa Associated Lymphoid Tissue (MALT) Lymphoma (NCT01015248; EUDRACT: 2008-007725-39).

The MALT 2008-01 trial was conducted in Spain by the Grupo Español de Linfomas/Transplante de Médula Ósea (GELTAMO) network and enrolled previously untreated patients aged from 18 to 85 years with biopsy proven CD20-positive MALT lymphoma at any extranodal site and in any stage. The primary outcome measure of the trial was EFS, and secondary measures included ORR, PFS, and OS, as well as acute and long-term toxicity.

Response adapted therapy included cycles given every 28 days of rituximab at 375mg/m² on day 1 and bendamustine at 90mg/m² on days 1 and 2. Patients who had achieved CR and PR after 3 cycles received one and three more cycles, respectively.

Key Highlights:

Patients:

• Overall, 60 pts were enrolled; 57 were evaluable
• Median age = 62 years (range, 26–84)
• Ann Arbor stage: I–II = 66%; III–IV = 34%
• Site of disease: stomach = 33%; extragastric = 57%; multifocal = 10%
• Presence of t(11;18)(q21;q21) identified in 9 pts (16%)

Efficacy:

• After 3 cycles, ORR = 100% (95% CI, 93–100); CR/uCR = 75%
• Pts with gastric involvement had significantly higher CR/uCR versus pts with non-gastric disease (90% vs 62%; P = 0.023)
• Fourteen pts (25%) did not achieve CR/uCR after 3 cycles and so went on to receive 6 cycles in total
• At end of therapy, ORR = 100%; CR/uCR = 98%
• Median observation time = 82 months (IQR, 75–90)
• 7-year EFS: in all pts = 87.7% (95% CI, 76.0–94.0%)
• 7-year EFS in gastric pts 89.5% (95% CI, 64.1–97.3%) versus4% (95% CI, 66.5–93.2%) in non-gastric pts; P = 0.637
• Estimated 7-year PFS = 92.8% (95% CI, 81.9–97.2%); relapses reported in 5 pts

Toxicity:

• In total, 264 cycles of therapy were administered
• Number of pts who experienced ≥1 grade 3–4 AE during therapy = 36 (60%)
• AEs were mostly hematological
• After 2 years of follow-up, three pts were reported to have opportunistic infections (1 herpes zoster, 1 cytomegalovirus, and 1 lung infection with Nocardia)
• So far, neoplasias have been reported in three pts: one Tongue Epidermoid Carcinoma, one Gastrointestinal Stromal Tumor, and one Granular Lymphoproliferative Disorder of NK-Cells
• Three pts developed Non-Melanoma Skin Cancers
• No deaths reported during therapy; three deaths reported during follow-up due to causes unrelated to Lymphoma (n=2) and DLBCL transformation (n=1)

Previously, the Lymphoma Hub reported on a new simple and effective prognostic tool (MALT-IPI) generated based on data from the phase III IELSG-19 trial (read more here). The authors of the current trial applied MALT-IPI to their patient cohort and it identified three risk groups with significantly different 7-year EFS (96%, 88%, and 50%) as well as PFS (100%, 91.8%, 66.7%).

The authors also compared their results to those of the IELSG-19 trial, which investigated the combination of rituximab and chlorambucil. This achieved a CR of 91% and 72% in gastric and non-gastric patients, respectively, which the authors note is lower that what they reported with rituximab and bendamustine. The group also drew attention to the fact that with rituximab and chlorambucil in the IELSG-19 trial, the time on treatment was 22 weeks compared to 16 weeks with rituximab and bendamustine and so is a more convenient option for patients.

In conclusion, the authors stated that rituximab plus bendamustine demonstrated “extremely good efficacy with excellent short and long-term outcomes” as first-line response-adapted therapy for MALT Lymphoma at any site or stage. The authors also noted that the regimen was tolerable, potentially due to its short duration in the majority of patients.

Abstract:

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