AFFILIATIONS
1 Memorial Sloan Kettering Cancer Center, New York, New York, United States
2 Memorial Sloan Kettering Cancer Center, New York, New York, United States, Memorial Sloan Kettering Cancer Center, New York, New York, United States, SUNY Downstate Health Sciences University, Brooklyn, New York, United States
3 University of Miami Miller School of Medicine, Miami, Florida, United States
4 Memorial Sloan Kettering Cancer Center, New York, New York, United States
5 Memorial Sloan Kettering Cancer Center, New York, New York, United States, Memorial Sloan Kettering Cancer Center, New York, New York, United States
6 Memorial Sloan Kettering Cancer Center, New York, New York, United States, Memorial Sloan Kettering Cancer Center, New York, New York, United States
7 Memorial Sloan Kettering Cancer Center, New York, New York, United States, Memorial Sloan Kettering Cancer Center, New York, New York, United States, Memorial Sloan Kettering Cancer Center, New York, New York, United States
8 Memorial Sloan Kettering Cancer Center, New York, New York, United States, Memorial Sloan Kettering Cancer Center, New York, New York, United States, Memorial Sloan Kettering Cancer Center, New York, New York, United States
9 Memorial Sloan Kettering Cancer Center, New York, New York, United States, Memorial Sloan Kettering Cancer Center, New York, New York, United States
10 Memorial Sloan Kettering Cancer Center, New York, New York, United States, Memorial Sloan Kettering Cancer Center, New York, New York, United States, Memorial Sloan Kettering Cancer Center, New York, New York, United States
11 Memorial Sloan Kettering Cancer Center, New York, New York, United States
12 Memorial Sloan Kettering Cancer Center, New York, New York, United States
13 Memorial Sloan Kettering Cancer Center, New York, New York, United States
14 Memorial Sloan Kettering Cancer Center, New York, New York, United States
15 Memorial Sloan Kettering Cancer Center, New York, New York, United States, Memorial Sloan Kettering Cancer Center, New York, New York, United States, Memorial Sloan Kettering Cancer Center, New York, New York, United States, Memorial Sloan Kettering Cancer Center, New York, New York, United States
16 Memorial Sloan Kettering Cancer Center, New York, New York, United States, Memorial Sloan Kettering Cancer Center, New York, New York, United States, Memorial Sloan Kettering Cancer Center, New York, New York, United States
17 Memorial Sloan Kettering Cancer Center, New York, New York, United States, Memorial Sloan Kettering Cancer Center, New York, New York, United States
18 Memorial Sloan Kettering Cancer Center, New York, New York, United States
19 Memorial Sloan Kettering Cancer Center, New York, New York, United States, Memorial Sloan Kettering Cancer Center, New York, New York, United States, Memorial Sloan Kettering Cancer Center, New York, New York, United States
ABSTRACT
Introduction
B-Cell maturation antigen directed CAR T has significantly improved treatment outcomes for relapsed/refractory multiple myeloma (RRMM). While early and deep hematological responses are associated with more durable remissions, little is known about the prognostic implications of the burden and distribution of persistent radiographic disease after CAR T. Hence, we sought to categorize the impact of residual radiographic and hematologic disease on subsequent patterns of radiographic progression. Moreover, to identify opportunities for integration of local consolidative radiotherapy, we associated the characteristics of persistent radiographic disease with the patterns of subsequent radiographic progression.
Methods
We performed a retrospective analysis of RRMM patients (pts) who received commercial cilta-cel and underwent FDG PET imaging 30 days (±14) post-infusion. We systematically assessed both hematologic and radiographic burden of disease at 30 days post CAR T. Radiographic response was assessed using Deauville-based criteria and lesions with SUV above the liver considered as active or PET avid. Hematologic response at day 30 was assessed by IMWG criteria, using 4 categories: complete response (CR), very good partial response (VGPR), partial response (PR), and stable disease (SD). For outcomes analysis, pts were binarily classified as having no radiographic disease or at least one avid lesion; and more granularly by number of avid lesions (0, 1, 2-5, >5) and site of avid lesions (bony, extramedullary [EM] or paramedullary [PM]). Pts were also classified as having residual hematologic disease if IMWG response was less than CR. For pts with subsequent disease progression, radiographic progression was defined as ≥ 30% SUV increase in a given lesion versus prior PET, or an increase in SUV from below to above liver level; hematologic progression was defined as per IMWG criteria. Progression free survival (PFS) and overall survival (OS) were defined from time of 30-day evaluation from cilta-cel infusion and were analyzed using log-rank testing.
Results
A total of 194 pts (median age 65) were included. Pts had received a median of 5 prior lines of therapy, 100% were triple-class exposed, 62% penta-class exposed, and 95% had prior transplant. 19% had EM disease, and 49% had high-risk cytogenetics. At median follow-up of 18 months, 2-year OS and PFS were 80% and 55%, respectively. A total of 66/194 pts (34%) had PET avid disease at day 30; 39 had bone-only disease and 27 had at least one PET avid EM or PM lesion. 32 (17%) had a single avid lesion. By IMWG criteria, 123/194 (63%) had residual hematologic disease; 72/194 (37%) achieved CR, 32 (16%) had VGPR, 51 (26%) had PR, and 39 (20%) had SD. A total of 41/194 pts (21%) had both PET avid and residual hematologic disease at Day 30.
While avid lesion number was associated with PFS (2-year PFS: 0: 61%; 1: 47%; 2-5: 43%; >5: 20%; p= 0.005), site of avid lesions (bone-only vs EM/PM present) was not associated with PFS (p=0.08). For pts with no residual hematologic disease (hematologic CR), presence of PET avid disease at day 30 was associated with inferior PFS (2-year PFS: No avid disease: 67%; Avid disease 45%; p=0.016). However, for pts with residual hematologic disease, no association was seen with residual radiographic disease (P= 0.4).
Overall, 25/66 (38%) pts with residual radiographic disease, and 29/128 (23%) without radiographic disease on day 30 progressed radiographically at the time of first disease progression. Patterns of progression were primarily at new sites, including for pts with solitary lesions (17 at new sites only, 4 at pre-existing sites only, 4 both), pts with bone-only disease (8 at new sites only, 2 at pre-existing sites only, 3 both), pts with EM/PM disease (9 new only, 2 pre-existing only, 1 both), and those achieving CR/VGPR with radiographic disease (7 new only, 2 pre-existing only, 4 both).
Conclusion
Presence of PET avid disease in pts with hematologic CR and number of avid lesions on day 30 post cilta-cel are associated with PFS, suggesting value for serial radiographic and serologic assessments in such pts. However, pattern of subsequent radiographic progression is heterogeneous and not necessarily enriched at pre-existing sites. This suggests that while PET avid disease burden at day 30 may have prognostic value, it does not reliably identify candidates for local consolidative therapy, even if combined with hematologic response.