MALT-IPI – a simple and effective tool generated from phase III IELSG-19 trial data

On 18th July 2017, Catherine Thieblemont from Saint Louis Hospital, Diderot University-Sorbonne Paris Cité, Paris, France, and colleagues published their study, which aimed to develop and validate a specific prognostic tool for Mucosa-Associated Lymphoid Tissue (MALT) Lymphoma, in the journal Blood.

The group used final analysis data from the international, randomized, phase III IELSG-19 trial (NCT00210353), which investigated chlorambucil versus rituximab versus chlorambucil plus rituximab in patients with MALT Lymphoma; the Lymphoma Hub reported on this trial earlier this year (read more here).

To develop a MALT Prognostic Index (MALT-IPI), 401 patients from IELSG-19 were analyzed. The median follow-up time was 7.4 years and 22.9% of patients (n=92) were aged over 70 years. Primary gastric MALT Lymphoma was diagnosed in 42.6% of patients (n=171), disseminated disease was observed at diagnosis in 43.6% (n=175), and 123 patients (30.7%) had more than one extranodal site. Lymph node involvement was observed in 35.4% of patients (n=142). Elevated Lactate Dehydrogenase (LDH) and poor Performance Status (PS) were uncommon (10.5% and 1.5%, respectively).

Key Highlights:
MALT-IPI elaboration:
  • A stepwise Cox regression including 400 pts with no missing data identified three independent predictors of shorter Event-Free Survival (EFS):
    • Ann Arbor stage III/IV: HR = 1.79
    • Age ≥ 70 years: HR = 1.72
    • Elevated LDH levels: HR = 1.87
  • MALT-IPI was built with three risk groups defined by the presence of 0 (low risk, n=167), 1 (intermediate risk, n=165), or ≥2 (high risk, n=68) of the three variables, respectively
  • The index distinguished pts with significantly different EFS and PFS, and also identified pts with significantly shorter OS and Cause-Specific Survival (CSS)
  • 5-year survival estimates for low, intermediate, and high risk pts:
    • EFS: 69.8% vs 7% vs 28.7% (P < 0.0001)
    • PFS: 76.0% vs 1% vs 32.5% (P < 0.0001)
    • CSS: 100% vs 1% vs 84.5% (P < 0.0001)
    • OS: 98.7% vs 1% vs 64.3% (P < 0.0001)
MALT-IPI evaluation:
  • In pts with gastric lymphoma, the number of low risk pts was significantly higher (52% vs 34%, P = 0.001) and the number of high risk pts was lower (12% vs 21%)
  • The model (n=400) retained its efficiency in distinguishing pts with poorer prognosis in both the gastric (n=171) and the non-gastric patient (n=229) subgroups
  • The model also maintained statistical significance in each treatment arm (chlorambucil, n=130; rituximab, n=138; R-chlorambucil, n=132) for all four survival endpoints
  • Histologic transformation occurred in 10 pts: 7 were high risk and 3 were intermediate risk according to the new MALT-IPI
External validation:
  • The validation set was created from three independent MALT Lymphoma cohorts (n=633): the IELSG-01 cohort, the Bellinzona-Novara cohort, and the MUV cohort
  • MALT-IPI retained its ability to significantly discriminate different prognostic groups with respect to each survival endpoint:
  • 5-year survival estimates for low, intermediate, and high risk pts:
    • EFS: 76.0% vs 4% vs 15.7% (P < 0.0008)
    • PFS: 56.8% vs 0% vs 22.7% (P < 0.0001)
    • CSS: 98.2% vs 7% vs 74.3% (P < 0.0001)
    • OS: 96.7% vs 7% vs 64.9% (P < 0.0001)
MALT-IPI compared to existing prognostic indices:
  • In the validation set (n=633), a definite risk group allocation was achieved in 87% of pts (n=551) according to the MALT-IPI, in 90% of pts (n=563) according to IPI, and in 90% of pts (n=564) according to R-IPI, respectively
  • The performance of all three models was very similar: MALT-IPI was slightly superior (highest k value) in the survival endpoint analysis; however, the standard errors indicate overlapping CI

The authors stated that MALT-IPI, which encompasses age 70 years or older, elevated LDH levels, and Ann Arbor stage III/IV, was validated in a large, external cohort of patients. They concluded that MALT-IPI is a “simple, accessible and effective tool” to aid the identification of high risk patients with MALT Lymphoma who are likely to experience disease relapse or death.


There are no widely accepted prognostic indices for extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma). This study aimed to develop and validate a specific prognostic tool to personalize and optimize lymphoma treatment of patients with MALT lymphoma. A prognostic index was built by Cox regression (stepwise selection) using data from 401 patients enrolled in the international randomized IELSG-19 trial (NCT 00210353). A validation set, including 633 patients, was obtained by merging three independent cohorts of MALT lymphoma patients. The three individual features maintaining the greatest prognostic significance for event-free survival (EFS, the main endpoint of the IELSG-19 trial) were age ≥70 years (HR 1.72, 95% CI 1.26-2.33), Ann Arbor stage III or IV (HR 1.79, 95% CI 1.35-2.38), and elevated LDH level (HR 1.87, 95% CI 1.27-2.77). The prognostic index (MALT-IPI) constructed using these three parameters identified three groups: low, intermediate and high risk (corresponding to the presence of 0, 1 or ≥2 of these factors, respectively). The 5-year EFS rates in the low, intermediate and high risk groups were 70%, 56% and 29%, respectively. The MALT-IPI also significantly discriminated between patients with different progression-free, overall and cause-specific survival. The prognostic utility was retained in gastric and non-gastric lymphomas, in each treatment arm (chlorambucil, rituximab, rituximab plus chlorambucil), and was confirmed in the validation set. The new index, MALT-IPI, is a simple, accessible and effective tool to identify MALT lymphoma patients at risk of poor outcomes. It may help define appropriate treatment approaches for individual patients.

  1. Thieblemont C. et al. A MALT lymphoma prognostic index generated from the dataset of the IELSG-19 prospective clinical trial. Blood. 2017 Jul 18. pii: blood-2017-03-771915. DOI: 10.1182/blood-2017-03-771915. [Epub ahead of print]