Less Aggressive Treatment Warranted for MCL With Primary GI Involvement

Grzegorz S Nowakowski, MD

Patients with mantle cell lymphoma (MCL) and primary gastrointestinal (GI) involvement have similar outcomes to those with secondary GI involvement, according to results from one of the largest known studies of GI MCL that was published in Blood Cancer Journal.

“The main implications of our research are that primary GI MCL is a rare and distinct presentation of MCL and it tends to be treated less aggressively, especially in patients with a lesser extent of GI involvement. However, we showed that it has a similar outcome to that of secondary GI MCL. Therefore, we can conclude that less aggressive treatment of primary GI MCL could be reasonable, even if it is still unknown how an intensified systematic treatment approach for these patients could result in better outcome,” Grzegorz S Nowakowski, MD, told Targeted Oncology, in an interview.

MCL is associated with both primary and secondary GI involvement. Secondary GI involvement is considered to be common in patients with MCL, occurring in 15% to 30% of patients. It has also been shown that it is detectable in roughly 90% of patients even without GI symptoms, hinting that it is even more prevalent than historical reports,. In terms of primary GI involvement, cases in MCL are rare, typically occurring in 4% to 9% of patients with primary GI non-Hodgkin lymphoma. The lack of research around the rare condition has left questions about the appropriate method of managing disease in these patients.

Investigators at the Mayo Clinic led by Nowakowski, consultant, Division of Hematology, Department of Internal Medicine, Mayo Clinic, evaluated data on 800 patients from the Mayo Clinic Lymphoma Clinical Database as well as the Molecular Epidemiology Resource (MER) from the University of Iowa/Mayo Clinic Lymphoma Specialized Program of Research Excellence. From these databases, demographic, clinical, and pathological characteristics were collected along with treatment and follow-up information.

Using a Chisquare or Fisher’s exact test, a comparison of baseline characteristics was conducted on patients with primary GI MCL versus patients with secondary GI MCL. The assessments focused on overall survival (OS) and progression-free survival (PFS), which were both determined by a Kaplan-Meir analysis. The prespecified threshold for statistically significant improvement in OS or PFS was a P-value <.05.

Comparing Primary and Secondary GI MCL

Of the patients included in the analysis, 2.8% had primary GI MCL, and 9.9% had secondary GI MCL. At baseline, 45.5% of the primary GI MCL group was ≤60 years of age compared with 38.0% of the secondary GI MCL group. The remaining 54.5% of the primary GI MCL cohort was >60 years old versus 62.0% of the secondary GI MCL group. In both GI involvement groups, the majority of patients were male, including 86.4% of the primary GI MCL cohort versus 83.5% of the secondary GI MCL cohort.

The ECOG performance status observed at baseline was <2 for most patients in the study, including 94.7% of the primary GI MCL cohort compared with 86.3% of the secondary GI MCL cohort. The remaining patients had an ECOG performance status of ≥2.

Overall, 14% of the patients included in the primary group and 19% in the secondary group had B symptoms at baseline. There were no patients with elevated lactate dehydrogenase (LDH) levels at baseline. Data on the GI symptoms that led to the diagnosis of GI MCL were available for 74% of the study population and included abdominal pain for 44% and GI bleeding for 31%. For the remaining 27% of patients, GI MCL was found during a routine colonoscopy screening.

In terms of lesion type, GI lesions were found as a single polyp, multiple polyps, mass lesion, or ulceration, erosion, or nodular lesion. In the cohort of patients with primary GI MCL, lesions were single polyp for 13.6%, multiple polyps for 63.6%, mass lesion for 9.1%, and either ulceration, erosion, or nodular lesion for 13.6%. In comparison, in the group of patients with secondary GI MCL, a single polyp was observed in 17.3 of patients, multiple polyps were seen in 33.2%, mass lesions in 21.3%, and either ulceration, erosion, or nodular lesion was observed in 22.7%. In terms of MCL involvement, the sites of disease were the colon (68%), small bowel (41%), stomach (32%), rectum (9%), and appendix (5%).

Overall, the results of the baseline characteristic analysis showed no distinct differences between patients with primary GI MCL and secondary GI MCL aside from lower LDH levels and lower MCL international prognostic index scores in the primary group.

Efficacy for GI MCL Based on Primary/Secondary Involvement

At a median follow-up of 85.0 months (95% CI, 53.4-116.6), patients with primary GI MCL had a median PFS of 32.5 months (95% CI, 21.4-43.6) compared with 38.5 months (95% CI, 22.9-54.2) in the secondary GI MCL cohort. At 5 years, the PFS rate observed in patients was 30.0% for primary GI MCL versus 28.1% for secondary GI MCL (P = .59).

The group of patients with primary GI MCL also had a median OS of 94.6 months (95% CI, 56.2-133.0) versus 136.1 months (95% CI, 39.3-233.0) in the secondary GI MCL group. Also, a 65.3% 5-year OS rate was seen in the primary GI MCL cohort versus 65.8% in the secondary GI MCL cohort (P­ = .83).

Overall, PFS (HR, 1.32; 95% CI, 0.67-2.57, P = .42) and OS (HR, 0.94; 95% CI, 0.37-2.42, P = .90) were similar between the groups. This result held true no matter the extent of GI involvement.

The data show encouraging support of less aggressive therapy, but Nowakowski also pointed out a subset of patients for which less aggressive therapy may not be as appropriate, stating: “From our research, we observed that the extent of GI involvement by primary GI MCL seemed to impact the treatment strategy, but not the outcomes. Patients with a single lesion were more likely to be observed or treated with surgery or radiation alone, while patients with multiple lesions (involving 1 or 2+ organs) were more likely to receive intensive systemic therapy and autologous stem cell transplant. The treatment outcomes were similar though in patients with different extent of GI involvement. This suggests that in patients with a lower disease burden, less aggressive/local initial treatment may be reasonable, reserving more aggressive and toxic treatment for relapse.”

“However, it is unknown whether upfront, more aggressive systemic treatment would improve long-term outcome. Basing on these data, we suggested that a more aggressive initial treatment would be anyway warranted in patients with primary GI MCL, but high tumor burden or documented multifocal disease at diagnosis, in which a localized treatment would inevitably lead to a relapse of disease,” Nowakowski added.

_References:

_{Nowacowski GS, Witzig TE, Ansell SM, et al. Clinical characteristics and outcomes of primary versus secondary gastrointestinal mantle cell lymphoma. Blood Cancer J. 2021;11:8. doi:10.1038/s41408-020-00394-z}