Friday, June 9, 2023
|
|
All (n = 238) |
D0-D30 (n = 54) |
D30-D90 (n = 102) |
>D90 (n = 82) |
|---|---|---|---|---|
|
Sex, male |
160 (67.2) |
37 (68.5) |
75 (73.5) |
48 (58.5) |
|
Age ≥65 y |
91 (38.2) |
29 (53.7) |
37 (36.3) |
35 (42.6) |
|
Histology |
||||
|
DLBCL, NOS |
178 (74.8) |
36 (66.7) |
82 (80.4) |
60 (73.3) |
|
PMBL |
11 (4.6) |
3 (5.6) |
2 (2.0) |
6 (7.3) |
|
HGBCL |
3 (1.3) |
2 (3.7) |
1 (1.0) |
0 (0) |
|
Transformed FL |
31 (13.0) |
7 (13.0) |
13 (12.7) |
11 (13.4) |
|
Other∗ |
15 (6.3) |
6 (11.1) |
4 (3.9) |
5 (6.1) |
| >3 lines of prior therapy
|
136 (57.1)
|
40 (74.1)
|
49 (48.0)
|
47 (57.3)
|
| Prior autologous transplant
|
46 (19.3)
|
9 (16.7)
|
21 (20.6)
|
16 (19.5)
|
|
ECOG PS at registration ≥2 |
28 (12.2) |
12 (23.1) |
13 (13.5) |
3 (3.7) |
|
LDH prior to infusion > UNL |
72 (38.9) |
31 (67.4) |
27 (35.1) |
14 (22.6) |
|
Bulky disease (>5 cm) |
53 (38.7) |
16 (51.6) |
24 (43.6) |
13 (25.5) |
|
aaIPI 2-3 |
126 (57.0) |
8 (15.7) |
7 (7.6) |
1 (1.3) |
|
Bridging therapy |
209 (87.8) |
49 (90.7) |
89 (87.2) |
71 (86.5) |
|
Neutropenia prior to infusion (<1 G/L) |
31 (13.5) |
9 (18.8) |
13 (13.0) |
9 (11.1) |
|
Lymphopenia prior to infusion (<1 G/L) |
168 (99.4) |
36 (100) |
73 (98.6) |
59 (100.0) |
|
Ferritin prior to infusion > UNL |
133 (84.7) |
37 (88.1) |
57 (85.1) |
39 (81.3) |
|
Median CRP prior to infusion, mg/L (range) |
20 (6-50) |
39 (0-349) |
18 (1-376) |
12.5 (0-204) |
| CAR T-cell product | ||||
|
Tisagenlecleucel |
102 (42.9) |
33 (61.1) |
40 (39.2) |
29 (35.3) |
|
Axicabtagene ciloleucel |
136 (57.1) |
21 (38.9) |
62 (60.7) |
53 (64.7) |
Table 1. Baseline patient and CAR T-cell therapy characteristics of all patients, according to timing of relapse/progression
Values are n (%), unless otherwise indicated.
aaIPI, age-adjusted International Prognostic Index; CRP, C-reactive protein; D, day; DLBCL, diffuse large B-cell lymphoma; ECOG PS, Eastern Cooperative Oncology Group performance status; FL, follicular lymphoma; HGBCL, high grade B-cell lymphoma; LDH, lactate dehydrogenase; NOS, not otherwise specified; PMBL, primary mediastina B-cell lymphoma; UNL, upper normal limit.
*3B-FL n = 2; primary central nervous system lymphoma n = 1; transformed marginal zone lymphoma n = 3; unclassifiable Hodgkin/DLBCL n = 9.
|
Treatment |
n = 154 |
|---|---|
|
IMID lenalidomide ∗ |
59 (38.3) |
|
Bispecific antibodies anti-CD20-CD3 |
11 (7.1) |
|
Target therapy † |
33 (21.4) |
|
Nivolumab |
11 (7.1) |
|
Pembrolizumab |
4 (2.6) |
|
Ibrutinib |
3 (1.9) |
|
Ibrutinib + lenalidomide + rituximab |
2 (1.3) |
|
Ibrutinib + corticosteroids |
2 (1.3) |
|
Ibrutinib + lenalidomide |
1 (0.6) |
|
Nivolumab + brentuximab vedotin |
1 (0.6) |
|
Pembrolizumab + lenalidomide |
1 (0.6) |
|
Lenalidomide + polatuzumab vedotin |
1 (0.6) |
|
Busulfan + fludarabine + nivolumab + thiotepa |
1 (0.6) |
|
Clinical trial LYM 1002‡ |
1 (0.6) |
|
MALT-1 inhibitor |
1 (0.6) |
|
Anti-CD20 monoclonal antibody |
3 (1.9) |
|
Other monoclonal antibody (anti-CD38, anti-CD30, anti-CD79b) |
1 (0.6) |
|
Radiotherapy |
17 (11.0) |
|
Immunochemotherapy |
31 (20.1) |
|
Palliative corticosteroids |
1 (0.6) |
Table 2. Treatments administered at CAR T-cell progression/relapse
Values are n (%). A total of 7% of patients (n = 17) did not receive any treatment because their disease was too advanced.
IMID, immunomodulatory drug; MALT-1, mucosa-associated lymphoid tissue lymphoma translocation protein 1.
∗Ten patients received lenalidomide alone; 49 received lenalidomide in combination, including 46 with rituximab.
†Among the 33 patients who received targeted therapies, 24 received monotherapy, and 9 received combination therapy (all with different drugs).
‡MALT-1 inhibitor + ibrutinib.
|
|
HR, 95% CI |
P |
|---|---|---|
|
Progression-free survival
|
||
|
LDH prior to infusion > UNL |
3.42 [1.93-6.05] |
<.0001 |
|
Progression/relapse D0-D30 |
1.74 [0.93-3.25] |
.0815 |
|
T-cell engagers |
NA |
.9878 |
|
Lenalidomide |
0.55 [0.29-1.07] |
.0789 |
|
Targeted therapy |
0.69 [0.33-1.45] |
.3228 |
|
Ferritin prior to infusion > UNL |
1.02 [1.00-1.03] |
.0173 |
|
Overall survival |
||
|
LDH prior to infusion > UNL |
2.10 [1.16-3.78] |
.0136 |
|
Progression/relapse D0-D30 |
2.93 [1.56-5.50] |
.0009 |
|
Bispecific antibodies |
0.22 [0.03-1.80] |
.1566 |
|
Lenalidomide |
0.42 [0.21-0.82] |
.0116 |
|
Targeted therapy |
0.47 [0.21-1.07] |
.0729 |
|
CRP prior to infusion > UNL |
1.11 [1.04-1.19] |
.0027 |
Table 3. Multivariable analysis of factors impacting survival outcomes of patients with aggressive B-cell lymphoma after failure of anti-CD19 CAR T-cell therapy
CI, confidence interval; CRP, C-reactive protein; D, day; HR, hazard ratio; LDH, lactate dehydrogenase; NA, not applicable; UNL, upper normal limit.
Physicians - maximum of 1.00 AMA PRA Category 1 Credit(s)™
ABIM Diplomates - maximum of 1.00 ABIM MOC points
This activity is intended for hematologists, oncologists, internists, and other physicians caring for patients with relapsed/refractory (R/R) aggressive B-cell non-Hodgkin lymphoma (BCL).
The goal of this activity is for learners to be better able to describe outcomes for 550 patients registered in DESCAR-T who progressed or relapsed after anti-cluster of differentiation (CD)19 chimeric antigen receptor (CAR) T-cell infusion; prognostic markers and post–CAR-T options for these patients; and the relationship between treatment strategies at relapse and outcomes after CD19 CAR-T failure.
Upon completion of this activity, participants will:
Medscape, LLC requires every individual in a position to control educational content to disclose all financial relationships with ineligible companies that have occurred within the past 24 months. Ineligible companies are organizations whose primary business is producing, marketing, selling, re-selling, or distributing healthcare products used by or on patients.
All relevant financial relationships for anyone with the ability to control the content of this educational activity are listed below and have been mitigated. Others involved in the planning of this activity have no relevant financial relationships.
Medscape, LLC designates this Journal-based CME activity for a maximum of 1.0
AMA PRA Category 1 Credit(s)™
. Physicians should claim only the credit commensurate with the extent of their participation in the activity.
Successful completion of this CME activity, which includes participation in the evaluation component, enables the participant to earn up to 1.0 MOC points in the American Board of Internal Medicine's (ABIM) Maintenance of Certification (MOC) program. Participants will earn MOC points equivalent to the amount of CME credits claimed for the activity. It is the CME activity provider's responsibility to submit participant completion information to ACCME for the purpose of granting ABIM MOC credit.
For questions regarding the content of this activity, contact the accredited provider for this CME/CE activity noted above. For technical assistance, contact [email protected]
There are no fees for participating in or receiving credit for this online educational activity. For information on applicability
and acceptance of continuing education credit for this activity, please consult your professional licensing board.
This activity is designed to be completed within the time designated on the title page; physicians should claim only those
credits that reflect the time actually spent in the activity. To successfully earn credit, participants must complete the
activity online during the valid credit period that is noted on the title page. To receive AMA PRA Category 1 Credit™, you must receive a minimum score of 70% on the post-test.
Follow these steps to earn CME/CE credit*:
You may now view or print the certificate from your CME/CE Tracker. You may print the certificate, but you cannot alter it.
Credits will be tallied in your CME/CE Tracker and archived for 6 years; at any point within this time period, you can print
out the tally as well as the certificates from the CME/CE Tracker.
*The credit that you receive is based on your user profile.
CME / ABIM MOC Released: 12/15/2022
Valid for credit through: 12/15/2023
processing....
Anti-CD19 chimeric antigen receptor (CAR) T-cells represent a major advance in the treatment of relapsed/refractory aggressive B-cell lymphomas. However, a significant number of patients experience failure. Among 550 patients registered in the French registry DESCAR-T, 238 (43.3%) experienced progression/relapse, with a median follow-up of 7.9 months. At registration, 57.0% of patients presented an age-adjusted International Prognostic Index of 2 to 3, 18.9% had Eastern Cooperative Oncology Group performance status ≥2, 57.1% received >3 lines of treatment prior to receiving CAR T-cells, and 87.8% received bridging therapy. At infusion, 66% of patients presented progressive disease, and 38.9% had high lactate dehydrogenase (LDH). Failure after CAR T-cell treatment occurred after a median of 2.7 months (range: 0.2-21.5). Fifty-four patients (22.7%) presented very early failure (day [D] 0-D30); 102 (42.9%) had early failure (D31-D90), and 82 (34.5%) had late (>D90) failure. After failure, 154 patients (64%) received salvage treatment: 38.3% received lenalidomide, 7.1% bispecific antibodies, 21.4% targeted treatment, 11% radiotherapy, and 20% immunochemotherapy with various regimens. Median progression-free survival was 2.8 months, and median overall survival (OS) was 5.2 months. Median OS for patients failing during D0-D30 vs after D30 was 1.7 vs 3.0 months, respectively (P = .0001). Overall, 47.9% of patients were alive at 6 months, but only 18.9% were alive after very early failure. In multivariate analysis, predictors of OS were high LDH at infusion, time to CAR-T failure <D30, and high C-reactive protein at infusion. This multicentric analysis confirms the poor outcome of patients relapsing after CAR T-cell treatment, highlighting the need for further strategies dedicated to this population.
Anti-CD19 chimeric antigen receptor (CAR) T cells are a major therapeutic advance in the management of patients with relapsed/refractory aggressive B-cell non-Hodgkin lymphoma (R/R aggressive BCL). Valuable response rates have been observed in both pivotal clinical trials (JULIET, ZUMA 1, and TRANSCEND) and real-world experience (Center for International Blood and Marrow Transplant Research; CAR T consortium registry; and French, Spanish, and German multicentric studies). Nonetheless, failure after CAR T-cell treatment remains a major issue, representing an unmet medical need. In the JULIET trial, nearly 60% of patients showed progression at 6 months after CAR T-cell infusion. [1] Similarly, the ZUMA 1 and TRANSCEND trials showed that approximately 50% of patients had relapsed at 6 months. [2-4]These data were confirmed in several real-world series. Pasquini et al reported the Center for International Blood and Marrow Transplant Research experience, with 60% failure at 6 months after tisagenlecleucel (tisa-cel) treatment.[5] Likewise, for axicabtagene ciloleucel (axi-cel), Nastoupil et al reported, in the US CAR T consortium registry, an approximate 45% failure rate after infusion.[6] Bethge et al reported in a German experience that 26% of patients presented progressive disease, with 64% of patients relapsing at 6 months.[7] In the Spanish report by Kwon et al, almost 30% of patients presented with failure after CAR T-cell treatment.[8] Iacoboni et al[9]showed an almost 70% relapse rate at 12 months in another Spanish cohort.
In a multicentric French study, more than half of the patients showed failure 6 months after CAR T-cell treatment.[10] These data were collected in the DESCAR-T (Dispositif d’Enregistrement et de Suivi des CAR-T) registry, a French national registry designed by the Lymphoma Study Association/Lymphoma Academic Research Organization (LYSA/LYSARC) to collect real-world data with commercial CAR T cells (axi-cel and tisa-cel) for up to 15 years after CAR T-cell infusion.[11]
The aim of the present study was to describe the outcome for patients registered in DESCAR-T who progress/relapse after CAR T-cell infusion, and to identify prognostic markers and post–CAR-T treatment options for this population. The relationship between treatment strategies at relapse, and the outcomes following CD19-CAR-T failure, was investigated in depth.
