Clinical Factors in MCL Successful in Guiding Watch-and-Wait Strategy

Anita Kumar, MD

Although biological criteria carry prognostic value in mantle cell lymphoma (MCL), initial observation based solely on clinical criteria was found to be an effective management strategy that did not compromise patient outcomes, according to a retrospective analysis published in Haematologica.¹

Patients who underwent a period of initial observation had superior overall survival (OS) compared with patients who were immediately treated. At a median follow-up of 44 months, the median rates of OS were 11.4 years and 9.4 years among patients in the observation and treatment arms, respectively (P = .043). However, there was no difference in outcome between arms from the start of treatment to death (P = .99). This suggests that the extended survival among patients who underwent initial observation is not a result of greater treatment sensitivity, but due to their more favorable clinical presentation and disease biology, noted first author Anita Kumar, MD, and investigators, in the publication.

“Our study confirms that initial expectant monitoring is an appropriate management strategy for MCL patients and is not associated with inferior outcomes,” wrote Kumar, a medical oncologist at Memorial Sloan Kettering Cancer Center, and colleagues.

To be eligible for enrollment, adult patients had to have a histologically confirmed diagnosis of MCL between 2000 and 2014 and received treatment at Memorial Sloan Kettering Cancer Center. Among 404 total patients, 90 underwent initial observation and 314 received immediate treatment.

Initial observation was defined as treatment deferral for ≥3 months following diagnosis as mandated by the treating physician. There were no predefined clinical or biological inclusion criteria for observation. Reasons for observation included lack of symptoms, low tumor burden, favorable biological features including low Ki-67 and SOX-11 negativity, leukemic phase disease without lymphadenopathy, or disease restricted to the gastrointestinal (GI) tract.

None of the patients recommended for observation had substantial constitutional symptoms, progressive marrow failure evidenced by anemia and/or thrombocytopenia, symptomatic organomegaly, progressive or symptomatic nodal enlargement, or evidence of clinically significant organ compression or involvement.

Patients were well balanced between arms in terms of age, sex, ECOG performance status, and bone marrow involvement. Among the observation and treatment arms, respectively, statistically significant differences regarding baseline characteristics included the presence of B symptoms (1% vs 17%), LDH> upper limit of normal (ULN; 9% vs 35%), extranodal involvement ≥2 sites (20% vs 32%), leukemic phase (26% vs 14%), histology (classic MCL [100% vs 89%] and blastic/blastoid/pleomorphic [0% vs 11%]), and Ki-67 index (<30% [75% vs 48%] and ≥30% [25% vs 52%]).

Among the 90 patients in the observation arm, 93% (n = 84) were successfully monitored for ≥6 months. Sixty-four patients proceeded with treatment after a period of observation, and 26 continued with their observation. The median time of observation was 23 months (95% CI, 17-28). In patients who were initially observed and then proceeded with treatment, 36% (n = 23) were observed for ≥12 months, 33% (n = 21) for 1 to 2 years, and 31% (n = 20) for ≥2 years.

In a univariate analysis, only lymphadenopathy measuring >1.5 cm, denoted a significantly shorter period of monitoring (HR, 2.15; 95% CI, 1.18-3.92; P = .01). Favorable Ki-67 status was not necessarily indicative of the length of observation as 15 patients with a Ki-67 ≥30% were observed for a median 22 months. Twenty-five patients received mutational analysis, revealing 3 patients with TP53 mutations (C242Y, G245C, and R290G); these patients were observed for 4, 18, and 20 months, respectively.

“In patients who harbor a genetic abnormality associated with resistance to cytotoxic anticancer drugs and shortened OS posttreatment, an initial phase of monitoring may critically prolong OS,” Kumar and colleagues wrote, citing a prior review of data. ²

Among patients who underwent observation for a period ≥2 years (n = 30), all were asymptomatic, the majority of whom had LDH within normal constraints at baseline. Moreover, patients had a low burden of lymphadenopathy, defined as the absence of either 3 lymph node sites ≥3 cm or any lymph node site ≥7 cm. Further, 93% (n = 28/30) of patients had a good Karnofsky performance score of ≥80%. However, 2 patients had poor baseline performance status due to frailty as a result of age and other comorbidities.

Within the observation cohort, 3 types of indolent MCL were monitored for ≥2 years: leukemic phase disease with minimal nodal disease, with or without splenomegaly (n = 9); low-tumor burden disease without leukemic phase disease (n = 17); and disease limited to the GI tract (n = 4).

“Collectively, these data reinforce the recommendation that the decision to initially monitor MCL patients should primarily be made based on clinical criteria, and even patients with high-risk biological factors, such as TP53 mutation or elevated proliferative index, may be appropriate candidates for initial monitoring,” the study authors concluded.

References

1. Kumar A, Ying Z, Alperovich A, et al. Clinical presentation determines selection of patients for initial observation in mantle cell lymphoma. Haematologica. 2019;104(4):e163-e166. doi: 10.3324/haematol.2018.201350.
2. Hientz K, Mohr A, Bhakta-Guha D, et al. The role of p53 in cancer drug resistance and targeted chemotherapy. Oncotarget. 2017;8(5):8921-8946. doi: 10.18632/oncotarget.13475.