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An expert panel hosted by
Customizing first-line BTK inhibitors for CLL
with Gilles Salles, Paolo Ghia, and Francesc Bosch
Wednesday, October 23, 2024
18:30-19:30 BST
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Despite recent efforts to improve outcomes, survival in patients with peripheral T-cell lymphoma (PTCL) remains poor. First-line treatment for the most common PTCL subtypes is anthracycline-based chemotherapy such as cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) or CHOP plus etoposide (CHOEP); these regimens achieve a cure in only 20–50% of patients. Furthermore, the majority of patients diagnosed with PTCL are aged 60 years or older, and so are generally less eligible for more intense therapies like autologous and allogeneic stem cell transplantation. Therefore, treatments with improved efficacy are needed for elderly patients with PTCL.
Anti-T-cell directed therapy, using the CD52 antigen expressed on normal lymphocytes and most T-cell lymphoma subtypes represents a potential target for therapy. Alemtuzumab, a recombinant humanized monoclonal antibody directed against CD52, showed promising results in three non-randomized phase II studies investigating alemtuzumab in combination with CHOP (A-CHOP) in patients with PTCL. Based on these findings, the phase III DSHNHL2006-1B/ACT2 trial (NCT00725231) was initiated in 52 study sites by the German Lymphoma Alliance (formerly known as German High-Grade Lymphoma Study Group), in collaboration with the Austrian Group of Medical Tumor Therapy, Lymphoma Study Association, France, Haemato Oncology Foundation for Adults in the Netherlands, and the Nordic Lymphoma Group, to evaluate A-CHOP in elderly patients with PTCL.
On May 7, 2020, the results of the trial were published in Leukemia by Gerald Wulf from the University Medical Center Göttingen, Germany, and colleagues, on behalf of the study investigators.1
Table 1. Selected baseline patient characteristics
A-CHOP, alemtuzumab and CHOP; AILT, angioimmunoblastic T-cell lymphoma; ALCL, anaplastic large cell lymphoma; ALK, anaplastic lymphoma kinase; CHOP, cyclophosphamide, doxorubicin, vincristine, and prednisone; ECOG, Eastern Cooperative Oncology Group; IPI, International Prognostic Index; PTCL-NOS, peripheral T-cell lymphoma not otherwise specified |
||
Characteristic |
A-CHOP (n = 58) |
CHOP (n = 58) |
---|---|---|
Sex, male/female, % |
66/34 |
50/50 |
Age, median (range) |
69 (60–80) |
69 (61–80) |
ECOG > 1, % |
21 |
19 |
Stage III/IV, % |
83 |
83 |
IPI > 3, % |
26 |
22 |
Bulky disease, % |
9 |
10 |
B-symptoms, % |
53 |
66 |
Subtype, % PTCL-NOS AILT ALK-negative ALCL Other |
38 45 6 12 |
24 45 7 24 |
Table 2. Hematological adverse events, Grade 3–4
A-CHOP, alemtuzumab and CHOP; CHOP, cyclophosphamide, doxorubicin, vincristine, and prednisone |
||
Event |
A-CHOP |
CHOP |
---|---|---|
Leukocytopenia, Grade 4 |
35/50 (70%) |
22/41 (54%) |
Thrombocytopenia, Grades 3 and 4 |
8/42 (19%) |
4/30 (13%) |
Anemia, Grades 3 and 4 |
17/58 (29%) |
11/57 (19%) |
Table 3. Treatment response
A-CHOP, alemtuzumab and CHOP; CHOP, cyclophosphamide, doxorubicin, vincristine, and prednisone; CR, complete remission; ORR, overall response rate |
||
Response |
A-CHOP (n = 58) |
CHOP (n = 58) |
---|---|---|
ORR, n (%) |
42 (72) |
38 (66) |
CR or unconfirmed CR, n (%) |
35 (60) |
25 (43) |
Partial response, n (%) |
7 (12) |
13 (22) |
The addition of alemtuzumab to CHOP increased response rates, but showed no improvement in survival. Furthermore, A-CHOP was associated with increased rates of infection, despite prophylactic measures, and secondary malignancies. The authors concluded that A-CHOP failed to improve the outcome for elderly patients with PTCL because the positive effects were outweighed by complications of alemtuzumab therapy. Of note, the estimated 5-year OS in the CHOP arm was 39%, which is in-line with that reported in registry-based observations, and reinforces the urgent need for improved treatment options in elderly patients with PTCL.1
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