Can combination chemotherapy after targeted therapy improve the efficacy of the initial treatment of patients with non-GCB diffuse large B-cell lymphoma?

Diffuse large B-cell lymphoma (DLBCL) is one of the most common lymphomas, accounting for two-fifths
of lymphomas worldwide.
The most common regimen for the new diagnosis of DLBCL is rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP), which cures approximately 60% of patients
.
However, 40% of patients are still refractory or relapse
after initial treatment.
DLBCL has a large molecular biology heterogeneity, and can be divided into germination center B cell type (GCB), activated B cell type (ABC) and indistinguishable subtypes
according to cell origin.
Patients with non-GCB (non-GCB) subtypes had poor
clinical outcomes after treatment with the R-CHOP regimen.

Studies have shown that both lenalidomide monotherapy and ibretinib monotherapy have a good effect
in patients with recurrent non-GCB DLBCL.
In addition, studies have shown good efficacy with rituximab, lenalidomide, and ibratinib (RLI) in patients with recurrent non-GCB DLBCL with a total response rate (ORR) of 65%, median progression-free survival (PFS) of 5.
5 months, ORR of 71% in combination with etoposide, doxorubicin, vincristine, prednisone, and cyclophosphamide (EPOCH), and a median PFS of 6.
5 months
。 Based on this, MD Anderson Cancer Center initiated an open-label, single-center Phase II clinical trial to understand the efficacy of RLI protocols in patients with initial treatment of non-GCB DLBCL
.

Inclusion criteria: (1) age ≥ 18 years; (2) Non-GCB DLBCL patients who have been diagnosed by immunohistochemistry (IHC) and have not received previous treatment; (3) ECOG physical fitness score ≤ 3 points
.

Medication regimen: patients with the 1st and 2nd courses of treatment are treated only with RLI regimen (rituximab 375mg/^m2, once on day 1; lenalidomide 25 mg, 1 time a day on days 1-10; Ibutinib 560 mg once a day for 21 days in a cycle), patients with courses 3-8 receive both RLI therapy and chemotherapy
.
Key study endpoints included ORR after 2 courses of RLI therapy and complete remission (CR) rates
at the end of all treatments.

• Clinical features

A total of 60 patients with non-GCB DLBCL (Table 1) were enrolled in this study, with a median age of 63.
5 years (range: 29-83 years) and 28% of patients ≥ 70 years
.
According to R-IPI, 42% (25/60) of patients are at higher risk
.
Of the patients tested for Ki-67, 45% (23/51) Ki-67 ≥ 90%.

13% of patients (8 patients) had R-IPI<3 and Ki-67 <80%.
<b13> MYC and BCL2 overexpression were detected by IHC, and 62% (24/39) of patients were double-expressed
.
The median time from diagnosis to treatment is 28 days (range: 9-138 days
).
Fifty-six patients underwent RLI combined chemotherapy, including 31 RLI+EPOCH and 25 RLI+CHOP
.

Table 1

• efficacy

After 2 courses of RLI therapy, 58 patients were able to assess efficacy with an ORR of 86.
2% (95% CI: 74.
6 to approximately 93.
9), a CR rate of 36.
2% (95% CI: 24.
0 to approximately 49.
9), and a partial response (PR) rate of 50% (Figure 1).

Figure 1

After 2 courses of RLI and 2 courses of RLI combined chemotherapy, 56 patients can assess efficacy with an ORR of 100% (95% CI: 93.
6 to about 100) and a CR rate of 75% (95% CI: 61.
6 to about 85.
6).

At the end of treatment, 55 patients were able to assess efficacy with an ORR of 100% (95% CI: 93.
5 to approximately 100) and a CR rate of 94.
5% (95% CI: 84.
9 to approximately 98.
9).

The median follow-up was 31 months (95% CI: 30 to approximately 40.
9), and the median PFS was not reached, with a 2-year PFS rate of 91.
3% (95% CI: 84.
3-98.
9).

The median OS was not reached, with a 2-year OS rate of 96.
6% (95% CI: 92-100
).
(Figure 2)

Figure 2

• security

The most common adverse events (AEs) were nausea, peripheral sensory neuropathy, diarrhea, and mucositis (Table 2
).
Other notable AEs are rash (grade 3: 16%), febrile neutropenia (38%), and atrial fibrillation (12%)
.

Table 2

The above findings show that RLI therapy combined with chemotherapy has a high remission rate and good survival outcomes
in patients with newly diagnosed DLBCL.
Targeted therapy in combination with chemotherapy after targeted therapy is feasible in the treatment of patients with DLBCL
.
RLI therapy results in higher ORR, and RLI combined chemotherapy provides lasting remission
.

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