A subgroup of poor risk patients with DLBCL who achieve CR by PET-CT can be identified using NCCN-IPI and COO

This month in Medical Oncology, Yusuke Kanemasa from the Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Honkomagome, Bunkyo-ku, Tokyo, Japan, and colleagues reported results of a retrospective study investigating the prognostic value of CR defined by PET-CT versus CT alone in patients with DLBCL. In addition to this, the group stratified patients by NCCN-IPI and COO to evaluate their ability to predict survival outcomes.

Records of 185 patients with de novo DLBCL (diagnosed from September 2004 to March 2015), treated with R-CHOP/R-CHOP-like regimens for ≥6 cycles, and achieved a CR defined by either CT alone or PET-CT at the end of therapy were included in the analysis. The median age of eligible patients was 68 years (range, 27–90 years) and the median number of chemotherapy cycles was 8 (range, 6–8). The median length of follow-up was 37 months for censored cases.

Key Highlights:

• Prognostic significance
  • CR defined by PET-CT = 61.6% (114 pts); CR defined by CT alone = 38.4% (71 pts)
  • Characteristics well balanced between two groups, only significantly differed in age (66yrs vs 70yrs in PET-CT and CT only groups, respectively; P = 0.038)
  • 5-yr PFS in pts with CR defined by PET-CT versus CT alone = 81.4% vs 2% (P = 0.009)
  • 5-yr OS in pts with CR defined by PET-CT versus CT alone = 87.5% vs 4% (P = 0.003)
  • Multivariate analysis found that age, stage, LDH, and CR defined by PET-CT were significantly associated with OS
• Stratification by NCCN-IPI
  • High risk category pts: 5-yr OS = 61.8%; 5-yr PFS = 53.8%
  • Low risk category pts: 5-yr OS = 100.0%; 5-yr PFS = 100.0%
  • Low-intermediate risk category pts: 5-yr OS = 89.7%; 5-yr PFS = 88.1%
  • High-intermediate risk category pts: 5-yr OS = 93.5%; 5-yr PFS = 80.4%
• Stratification by COO
  • Determined in 146 pts; GCB = 67; non-GCB = 79
  • Pts with CR by PET-CT: GCB = 40; non-GCB = 57
  • 5-year OS in pts with CR by PET-CT with GCB versus non-GCB DLBCL = 96.9% vs 5% (P = 0.039)
  • 5-yr PFS in pts with CR by PET-CT with GCB versus non-GCB DLBCL = 94.8% vs 2% (P = 0.017)
• Sites of relapse
  • Relapse occurred in 36 pts (19.5%), 15 had achieved CR by PET-CT, 21 had achieved CR by CT alone
  • Pts with CR by PET-CT were significantly more likely to relapse at new sites than pts with CR by CT alone (80% vs 1%; P = 0.024)

This retrospective study found that patients who achieved CR defined by CT alone had significantly worse PFS and OS than those who achieved CR defined by PET-CT. However, a non-negligible number (13.2%) of patients who obtained CR defined by PET-CT did relapse. In terms of stratification by NCCN-IPI, high risk patients had a poor outlook despite obtaining CR defined by PET-CT, but patients with low, low-intermediate, and high-intermediate risk had good outcomes. Moreover, based on COO, patients with GCB rather than non-GCB DLBCL had significantly better outcomes. The authors of this analysis concluded that a subgroup of poor risk patients who achieve PET-CT CR can be identified using NCCN-IPI and COO.

Abstract:

Positron emission tomography-computed tomography (PET-CT) is performed as the standard method for response assessment of diffuse large B cell lymphoma (DLBCL) patients. However, a substantial proportion of patients experience relapse even if they have achieved complete response (CR) defined by PET-CT. We validated the prognostic value of CR by PET-CT and applied the National Comprehensive Cancer Network-International Prognostic Index (NCCN-IPI) and cell of origin (COO) to patients with CR by PET-CT to evaluate their additional predictive ability for survival outcomes. We retrospectively analyzed DLBCL patients who were treated with R-CHOP or an R-CHOP-like regimen and who achieved CR by PET-CT or CT only. A total of 185 patients were analyzed: 114 patients achieved CR by PET-CT and 71 patients by CT only. Patients with CR by PET-CT had significantly better overall survival (OS) than those with CR by CT (5-year OS, 87.5 vs. 62.4%, P = 0.003). Patients with high risk according to the NCCN-IPI had a dismal outcome despite achieving CR by PET-CT (5-year OS, 61.8%). In contrast, low-, low-intermediate-, and high-intermediate-risk patients had excellent outcomes (5-year OS, 100, 89.7, and 93.5%, respectively). Among patients with CR by PET-CT, patients with germinal center B cell (GCB) DLBCL (n = 40) had significantly better survival than those with non-GCB DLBCL (n = 57) (5-year OS, 96.9 vs. 75.5%, P = 0.039). We demonstrated that CR by PET-CT was a better predictor of survival outcomes than CR by CT only. The NCCN-IPI and COO subtypes could identify a subpopulation of poor-risk patients among those who achieved CR by PET-CT.