On Location
The Latest in Lymphomas
NEWS
The 2021 International Conference on Malignant Lymphoma ( ICML ) was held virtually June 18-22 . Here , we report on some of the most recent data on lymphoid neoplasms : an experimental response-adapted rituximab approach to follicular lymphoma and results from the GELTAMO ICML-2015 study evaluating ibrutinib plus rituximab for indolent mantle cell lymphoma .
Evaluating a Response-Adapted Rituximab Approach for Patients With Follicular Lymphoma
In patients with follicular lymphoma ( FL ), standard rituximab maintenance produced better rates of progression-free survival ( PFS ) than an experimental response-adopted approach , according to results of the FOLL12 study presented at ICML 2021 . The findings were shared by lead author Stefano Luminari , MD , from the University of Modena and Reggio Emilia in Italy .
While previous research has shown that two years of rituximab maintenance after first-line rituximab-based chemotherapy significantly improved PFS in this group , the study authors explained that one important question is whether this approach is suitable for all patients .
In this study , researchers randomized patients with treatment-naïve , advanced stage , high tumor burden FL to receive standard rituximab maintenance or a response-adapted rituximab based on metabolic response and molecular assessment of measurable residual disease ( MRD ). Complete metabolic response at end of induction was defined as a Deauville score of 1-3 .
Post-induction therapy in the experimental arm varied according to patient status :
• complete molecular response ( CMR ) and MRD negativity : observation
• CMR and MRD positivity : 4 weekly rituximab doses until reaching MRD negativity , for up to 3 courses
• no CMR : one dose of ibritumomab tiuxetan followed by standard rituximab maintenance
A total of 712 study participants across both groups achieved at least a partial response at the end of induction . After a median follow-up of 53 months ( range = 1-92 ), patients in the standard arm had significantly higher rates of three-year PFS than those who received the experimental approach : 86 % versus 72 % ( p < 0.001 ).
This finding was confirmed across all response subgroups , the authors added . Rates of three-year PFS in the standard arm versus the experimental arm were :
• 90 % vs . 72 % in patients who achieved a CMR ( p < 0.001 )
• 92 % vs . 78 % in patients with CMR and MRD negativity ( p < 0.001 )
• 96 % vs . 45 % in patients with CMR and MRD positivity ( p = 0.004 )
However , there was no significant difference with either approach in patients without CMR .
At the latest follow-up , 30 patient deaths were reported . Half of these were related to disease progression or recurrence . The three-year rate of overall survival was 98 % in the standard arm and 97 % in the experimental arm ( p = 0.238 ).
Together , the findings of this analysis suggest that a post-induction rituximab strategy according to metabolic and molecular response was associated with a significantly inferior PFS compared to standard two-year rituximab maintenance .
Ibrutinib Plus Rituximab Shows Efficacy in Indolent Mantle Cell Lymphoma
In the GELTAMO ICML-2015 study , treatment with frontline ibrutinib in combination with rituximab demonstrated high rates of efficacy in patients with indolent mantle cell lymphoma ( MCL ), with promising rates of measurable residual disease ( MRD ) negativity . The combination also had a predictable toxicity profile , according to study presented by Eva Giné , MD , from the Hospital Clínic de Barcelona in Spain , at ICML 2021 .
The GELTAMO ICML-2015 study is a multicenter , single-arm , open-label , phase II trial that enrolled 50 patients with previously untreated MCL who met the following criteria : no symptoms attributable to MCL , Eastern Cooperative Oncology Group score of 0-1 , stable disease without a need for therapy for at least three months , non-blastoid variants , Ki-67 < 30 %, and largest tumor diameter ≤3 cm .
Participants received ibrutinib 560 mg daily and a total of eight doses of rituximab 375 mg / m 2 ( 4 weekly doses during the first 28-day cycle , followed by day 1 of cycles 3 , 5 , 7 , and 9 ). Per study protocol , ibrutinib could be discontinued after two years of treatment if the patient experienced sustained undetectable MRD .
After a median follow-up of 33 months , four patients discontinued treatment early due to adverse events ( AEs ). The overall response rate was 84 %, which included a complete response ( CR ) rate of 80 %. Among the 45 patients who were evaluable for MRD , the rate of MRD negativity in peripheral blood was 86 % and 64 % in bone marrow . In those who experienced CR , 72 % had undetectable MRD in both peripheral blood and bone marrow .
Nineteen patients discontinued treatment
“ The better efficacy of standard rituximab maintenance was confirmed in the subgroup analysis and in particular for patients achieving both CMR and MRD negativity ,” they added .
Study authors report no relevant conflicts of interest .
Reference Luminari S , Galimberti S , Versari A , et al . Response adapted post induction therapy in follicular lymphoma : updated results of the FOLL12 trial by the Fondazione Italiana Linfomi ( FIL ). Presented at the 16th International Conference on Malignant Lymphoma , Virtual Edition , June 18-22 , 2021 .
after 24 months because they were in response and had undetectable MRD . Four patients experienced progressive disease at 12 , 38 , 40 , and 52 months of follow-up , respectively ; two of them eventually died due to disease progression .
Overall , the estimated progression-free and overall survival rates at 42 months were 81 % and 86 %, respectively . Five patients withdrew from the study due to serious AEs , including skin rash , severe aplastic anemia , pancreatic adenocarcinoma , lumbar fractures , and patient decision ( n = 1 for all ). The most common treatment-related AEs were diarrhea ( 38 %), neutropenia ( 36 %), fatigue ( 32 %), upper respiratory infection ( 26 %), nausea ( 22 %), and arterial hypertension ( 20 %). The authors added that 10 patients had discontinued ibrutinib due to tolerance as of last follow-up .
Given the acceptable toxicity profile , Dr . Giné and colleagues noted that this is a promising combination for patients with MCL , particularly because it demonstrated efficacy with a limited duration of two years , rather than indefinite treatment . ●
Study authors report no relevant conflicts of interest .
Reference Giné E , De La Cruz F , Ubieto J , et al . Efficacy and safety of ibrutinib in combination with rituximab as frontline treatment for indolent clinical forms of mantle cell lymphoma . Results of the GELTAMO ICML-2015 study . Presented at the 16th International Conference on Malignant Lymphoma , Virtual Edition , June 18-22 , 2021 .
Check out online exclusives at www . ashclinicalnews . org
36 ASH Clinical News August 2021