Abstract
Background:
Ibrutinib (IBR) is an oral covalent Bruton tyrosine kinase inhibitor (BTKi), licensed for treatment of relapsed or
refractory mantle cell lymphoma (MCL). Under NHS interim Covid-19 agreements in England, IBR with or without
rituximab (R) was approved for the frontline treatment for MCL patients (pts) as a safer alternative to conventional
immunochemotherapy. Although recent phase 2 studies have reported high response rates in low-risk patients for this
combination in the frontline setting, randomised phase 3 and real-world data are currently lacking.
Aims:
To describe the real-world response rates (overall response rate (ORR), complete response (CR) rate) and toxicity
profile of IBR +/- R in adult patients with previously untreated MCL.
Methods:
Following institutional approval, adults commencing IBR +/- R for untreated MCL under interim Covid-19
arrangements were prospectively identified by contributing centres. Hospital records were interrogated for
demographic, pathology, response, toxicity and survival data. ORR/CR were assessed per local investigator according to the Lugano criteria using CT and/or PET-CT.
Results:
Data were available for 66 pts (72.7% male, median age 71 years, range 41-89). Baseline demographic and clinical
features are summarised in Table 1. 23/66 pts (34.8%) had high-risk disease (defined as presence of TP53
mutation/deletion, blastoid or pleomorphic variant MCL, or Ki67%/MiB-1 ≥30%). IBR starting dose was 560mg in
56/62 pts (90%) and was given with R in 22/64 pts (34%). At a median follow up of 8.7 months (m) (range 0-18.6),
pts had received a median of 7 cycles of IBR. 19/60 pts (32%) required a dose reduction or delay in IBR treatment.
New atrial fibrillation and grade ≥3 any-cause toxicity occurred in 3/59 pts (5.8%) and 8/57 (14.0%) respectively.
For the whole population and high-risk pts only, ORR was 74.4% and 64.7% respectively (p=0.2379), with a median
time to response of 3.8m, coinciding with the first response assessment scan. Seven pts (16.7%), of whom 2 had highrisk disease, attained CR at a median of 6.0m. ORR for pts receiving vs not receiving R were 84.2% and 66.7%
respectively (p=0.1904). IBR was discontinued in 20/61 pts (32.8%) at a median time to discontinuation of 4.1m, due
to progressive disease (PD, 19.7%), toxicity (4.9%), death (3.3%; 1 pt each of Covid-19 and E. coli infection), pt
choice (3.3%) and other unspecified reasons (1.6%). 15/66 pts (22.7%) overall and 7/23 (30.4%) with high-risk
disease progressed on IBR at a median time to PD of 4.0m. No pts underwent autologous stem cell transplantation
consolidation during the study period. 12/57 pts (21.1%) received second line treatment (R-chemotherapy n=7, Nordic MCL protocol n=2, VR-CAP n=2, pirtobrutinib n=1). Response to second line treatment was CR in 4/11 pts,
PD in 7/11. Of the 2 Nordic-treated patients, 1 had CR after cycle 2 and 1 PD. Fourteen pts (21.2%) died during the
follow up period, due to MCL (n=11), Covid-19 (n=2) and congestive cardiac failure (n=1). Overall survival was
lower for patients with high-risk disease (HR 0.55, p=0.038).
Summary/Conclusion:
In this real-world UK cohort of pts receiving first-line IBR +/-R for MCL, including older and high-risk pts, we report
high ORR rates in a similar range to the phase II Geltamo IMCL-2015 study of combination IBR-R in an exclusively
low-risk population. Documented CR rates were lower, possibly reflecting a low usage of rituximab in the Covid-19
pandemic as well as CT assessment of response. Treatment was generally well tolerated, with low rates of toxicity- related treatment discontinuation. The study is ongoing.
Ibrutinib (IBR) is an oral covalent Bruton tyrosine kinase inhibitor (BTKi), licensed for treatment of relapsed or
refractory mantle cell lymphoma (MCL). Under NHS interim Covid-19 agreements in England, IBR with or without
rituximab (R) was approved for the frontline treatment for MCL patients (pts) as a safer alternative to conventional
immunochemotherapy. Although recent phase 2 studies have reported high response rates in low-risk patients for this
combination in the frontline setting, randomised phase 3 and real-world data are currently lacking.
Aims:
To describe the real-world response rates (overall response rate (ORR), complete response (CR) rate) and toxicity
profile of IBR +/- R in adult patients with previously untreated MCL.
Methods:
Following institutional approval, adults commencing IBR +/- R for untreated MCL under interim Covid-19
arrangements were prospectively identified by contributing centres. Hospital records were interrogated for
demographic, pathology, response, toxicity and survival data. ORR/CR were assessed per local investigator according to the Lugano criteria using CT and/or PET-CT.
Results:
Data were available for 66 pts (72.7% male, median age 71 years, range 41-89). Baseline demographic and clinical
features are summarised in Table 1. 23/66 pts (34.8%) had high-risk disease (defined as presence of TP53
mutation/deletion, blastoid or pleomorphic variant MCL, or Ki67%/MiB-1 ≥30%). IBR starting dose was 560mg in
56/62 pts (90%) and was given with R in 22/64 pts (34%). At a median follow up of 8.7 months (m) (range 0-18.6),
pts had received a median of 7 cycles of IBR. 19/60 pts (32%) required a dose reduction or delay in IBR treatment.
New atrial fibrillation and grade ≥3 any-cause toxicity occurred in 3/59 pts (5.8%) and 8/57 (14.0%) respectively.
For the whole population and high-risk pts only, ORR was 74.4% and 64.7% respectively (p=0.2379), with a median
time to response of 3.8m, coinciding with the first response assessment scan. Seven pts (16.7%), of whom 2 had highrisk disease, attained CR at a median of 6.0m. ORR for pts receiving vs not receiving R were 84.2% and 66.7%
respectively (p=0.1904). IBR was discontinued in 20/61 pts (32.8%) at a median time to discontinuation of 4.1m, due
to progressive disease (PD, 19.7%), toxicity (4.9%), death (3.3%; 1 pt each of Covid-19 and E. coli infection), pt
choice (3.3%) and other unspecified reasons (1.6%). 15/66 pts (22.7%) overall and 7/23 (30.4%) with high-risk
disease progressed on IBR at a median time to PD of 4.0m. No pts underwent autologous stem cell transplantation
consolidation during the study period. 12/57 pts (21.1%) received second line treatment (R-chemotherapy n=7, Nordic MCL protocol n=2, VR-CAP n=2, pirtobrutinib n=1). Response to second line treatment was CR in 4/11 pts,
PD in 7/11. Of the 2 Nordic-treated patients, 1 had CR after cycle 2 and 1 PD. Fourteen pts (21.2%) died during the
follow up period, due to MCL (n=11), Covid-19 (n=2) and congestive cardiac failure (n=1). Overall survival was
lower for patients with high-risk disease (HR 0.55, p=0.038).
Summary/Conclusion:
In this real-world UK cohort of pts receiving first-line IBR +/-R for MCL, including older and high-risk pts, we report
high ORR rates in a similar range to the phase II Geltamo IMCL-2015 study of combination IBR-R in an exclusively
low-risk population. Documented CR rates were lower, possibly reflecting a low usage of rituximab in the Covid-19
pandemic as well as CT assessment of response. Treatment was generally well tolerated, with low rates of toxicity- related treatment discontinuation. The study is ongoing.
| Original language | English |
|---|---|
| Article number | P1141 |
| Pages (from-to) | 1985-87 |
| Number of pages | 3 |
| Journal | HemaSphere |
| Publication status | Published - Jun 2022 |
| Event | EHA 2022 Congress - Vienna Duration: 15 Jun 2022 → 17 Aug 2022 |
Research Beacons, Institutes and Platforms
- Manchester Cancer Research Centre
