Chemo-Free Salvage Treatment Is Better Than Traditional Chemotherapy in Relapsed/Refractory Subcutaneous Panniculitis-like T-Cell Lymphoma

Introduction:

Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a rare subtype of non-Hodgkin lymphoma which predominantly localizes in the subcutaneous adipose tissue, which was estimated to account for 1-2% of cutaneous lymphoma cases. It has a low disease control rate and high relapse rate, which necessitate further investigations on relapse or refractory (R/R) SPTCL. However, few studies reviewing SPTCL have focused on R/R SPTCL treatment regimens. This study retrospectively studied R/R SPTCL in China, to discribe the clincal characteristic of R/R SPTCL and compared efficacy of chemo-free and chemotherapy.

Methods:

Patients who were diagnosed as R/R SPTCL between September 1997 and October 2020 in Peking Union Medical College Hospital were included. Survival were analyzed using the method of Kaplan-Meier, and statistical comparison was done by log-rank testing. All reported p-values are two-sided, and values of p<0.05 were considered significant. Relationships between subgroups were examined by Pearson test or the Fisher exact test, where appropriate. Statistical analyses were performed with SPSS 20.0.

Results:

Sixteen primary refractory patients and three first relapsed patients of them were included in this study. The median age was 34 years, 9 patients (47.4%) were male, and 7 patients (36.8%) had concurrent hemophagocytic lymphohistiocytosis (HLH). All patient recieved chemotherapy-based treatment as the first-line treatment. The median follow-up time was 95.1 months and the median PFS of first-line treatment were 1.8 months.

Sixteen patients received salvage therapies. In the second-line treatment, the ORR was 31.3% and the median PFS was 3.0 months. Patient 1 and Patient 5 received allo-HSCT and achieved CR. The PFS was 131.4 and 105.3 months. Patient 8 received cyclosproin A (CsA) plus interferon α (IFN α) regimen, achieved stable disease (SD) and relapsed 3.4 months later. Patient 16 achieved CR after accepting VRMP regimen but relapsed 4.1 months later due to the patient's discontinuation of medication on her own initiative. The other 12 patients accepted chemotherapy-based treatment. The ORR of these patients were 25% and the median PFS was 1.4 months. Only Patient 13 who received bortezomib plus GDP (gemcitabin, cisplatin and dexamethasone) regimen achieved CR and has not relapsed with a PFS of 120.3 months.

Fourteen patients received a third-line treatment. The ORR was 71.4% and the median PFS was 138.8 months. Seven patients accepted chemotherapy-based regimen and six patients accepted chemo-free regimen such as VRMP (bortezomib, lenadomide and methylprednisolone) regimen and CsA plus IFNα regimen. Only Patient 5 recevied second allo-HSCT after relapse of first allo-HSCT in second-line treatment. In chemotherapy group, all patients relapsed and 4 of them died of lymphoma progression. Patient 5 achieved CR and did not relapse until last follow-up. In chemo-free group, 3 patients received VRMP regimen treatment, all of whom had concurrent HLH. The other 3 patients received CsA plus IFNα regimen. All patient in chemo-free group achieved CR or PR and did not relapse until last follow-up. The median PFS of chemotherapy group was 3.2 months and the median PFS of chemo-free group was not reached. Chemo-free group had a better PFS than chemotherapy group (p=0.007).

4 patients finally died in the follow-up owing to disease progression at the third-line chemotherapy treatment. The median OS and the OS rate of all patients receiving salvage treatment were 147.5 months and 75%. The median OS were found to be 147.5 months and not reached in the chemotherapy and chemo-free groups, respectively. The 1-year OS rates of two groups were 57.1% vs 100%.

Univariate cox regression analysis found that using of chemo-free regimen in the third-line significantly prolong PFS of the third-line treatment. No significant predictor of OS was found.

Conclusions:

This is the largest single-center retrospective cohort of R/R SPTCL. For patients who failed in the first-line conventional polychemotherapy, chemo-free regimen containing immunomodulatory drugs may be a better choice compared with cytotoxic chemotherapy. CsA and bortezomib-based regimen exhibited excellent efficacy and better outcome. This study had a long follow-up period, demonstrating the durability of immunomodulatory drugs. Despite of good clinical responses, more trials are warranted to validate our conclusions.

No relevant conflicts of interest to declare.