This combination regimen may improve outcomes for patients with relapsed/refractory mantle cell lymphoma in China

Clinical features

A total of 121 patients with R/R MCL were included in this study, including 68 in the monotherapy group and 53 in
the combination therapy group.
The proportion of patients aged 60 years in the combination group ≥ lower than in the monotherapy group (P=0.
033).

There were no statistically significant differences in other baseline features between the two groups (Table 1).

Table 1

Treatment plan and efficacy assessment

Forty-five patients (84.
9%) in the combination group were treated with no chemotherapy regimen
.
Ibrutinib + rituximab (IR) was the most common combination regimen (32/53, 60.
4%), followed by ibrutinib + rituximab + lenalidomide (IR2) (10/53, 18.
9%)
.
During the combination therapy, 8 patients experienced disease progression, and the remaining 45 patients achieved at least SD after 4-8 courses of treatment, and no disease progression; 91.
1% (41/45) of patients received maintenance therapy
.
The optimal ORR of 121 patients was 71.
1%, the CR rate was 28.
1%, and the partial response (PR) rate was 43.
0%.

The ORR and CR rates in the combination treatment group were significantly higher than those in the monotherapy group (ORR, 84.
9% vs 60.
3%, P=0.
003; CR rate, 43.
4% vs 16.
2%, P<0.
001).

The ORR and CR rates of patients in the combination treatment group who received no chemotherapy regimen were 84.
4% and 44.
4%,
respectively.

The median TTRs were 6.
3 months (95% CI, 4.
6–8.
1 months) and 2.
6 months (95% CI, 2.
4–3.
5 months) in the monotherapy and combination groups, respectively (Figure 1).

Of the 86 patients who responded to treatment, the median DOR was 14.
8 months (95% CI, 11.
2 to 22.
7 months) in the monotherapy group and not in the combination group (Figure 2).

The difference between TTR and DOR was statistically significant (TTR, P<0.
001; DOR, P=0.
008).
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Figure 1

Figure 2

Survival analysis

With a median follow-up of 20.
5 months (95% CI, 18.
3 to 22.
6 months), the estimated median PFS for all patients was 21.
7 months (95% CI, 15.
2 to 26.
6 months), and the PFS rates at 1 and 2 years were 70.
7% and 39.
5%,
respectively.
The median OS was 37.
6 months, with 1-year and 2-year OS rates of 86.
9% and 64.
2%,
respectively.
PFS was longer in the combination group than in the monotherapy group (30.
8 [95% CI, 23.
5-NE] vs 18.
5 [12.
1 to 21.
8]; HR，0.
53 [95% CI，0.
30-0.
93]； P=0.
025) (Figure 3).

Figure 3

OS was not improved in the combination group compared with monotherapy (median OS did not reach [95% CI, 20.
6-NE] vs 28.
2 months [95% CI, 21.
5-NE]; HR，0.
77[95% CI，0.
39-1.
55]； P = 0.
430) (Figure 4).

Figure 4

The PFS benefit of combination versus monotherapy was assessed in different subgroups based on baseline characteristics, with significant PFS benefit observed in male patients, non-refractory disease, Ki67<30%, previous treatment line = 1, ablastic subtype, and extranodal involvement site <2 (Figure 5).
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Figure 5

security

At the last follow-up, 67 patients discontinued ibrutinib-based therapy, mainly due to disease progression (50/67, 74.
6%)
.
Other reasons for discontinuation of ibrutinib included: treatment side effects (9/67, 13.
4%; 2 cases of pulmonary infection, 3 cases of hemorrhage, 3 cases of secondary tumors, 1 case of ventricular premature beats and palpitations), patient or physician choice (4/67, 6.
0%), non-MCL-related death (1/67, 1.
5%), and unknown cause (3/67, 4.
5%)
.

The incidence of neutropenia was significantly higher in the combination group than in the monotherapy group (32.
0% vs 12.
7%, P=0.
017).

Fifteen patients had abnormal ECG tests, of which 2 showed atrial fibrillation, the rest included 11 cases with atrial premature contractions, and 2 cases with premature ventricular beats
.
Heavy bleeding occurred in 4 patients, 1 case of central nervous system hemorrhage, 1 case of grade 3 gastrointestinal bleeding, and 1 case
of grade 3 subcutaneous hemorrhage.

Mutation analysis

In 21 available tumor samples, 446 leukemia and lymphoma-related genes were detected by NGS, and missense mutations were found to be the main type of
gene mutation.
The four genes with the highest mutation frequency were ATM (13/21, 61.
9%), KMT2D (8/21, 38.
1%), NSD2 (6/21, 28.
6%) and SMARCA4 (5/21, 23.
8%)
.