ORR: 55% (n=39; 95% CI: 43%, 67%)
CR: 37%
PR: 18%
L-MIND: AN OPEN-LABEL, MULTICENTER, SINGLE-ARM, PHASE 2 STUDY1,2
L-MIND study design1
- Efficacy and safety of MONJUVI in combination with lenalidomide followed by MONJUVI monotherapy were evaluated in adults with R/R DLBCL after 1 to 3 prior systemic DLBCL therapies, including a CD20-containing therapy
- Enrolled patients at the time of the trial were not eligible for or refused ASCT
- Efficacy was established in 71 patients with DLBCL, as assessed by an Independent Review Committee using the International Working Group Response Criteria (Cheson 2007)
Primary endpoint
Best overall response rate (ORR) (CR + PR)
Select secondary endpoint
Duration of response (DoR)
EACH CYCLE WAS 28 DAYS
Cycles 1 to 3
MONJUVI
12 mg/kg on days 1, 4*, 8, 15, 22
*Loading dose on day 4 is given in cycle 1 only.
Cycles 4 to 12
MONJUVI
12 mg/kg on days 1 and 15
Lenalidomide
25 mg/day by mouth on days 1 to 21 for up to 12 cycles
≥SD
Cycles 13+
MONJUVI
12 mg/kg on days 1 and 15
Until progression or unacceptable toxicity
Administer premedications, including acetaminophen, histamine H₁ receptor antagonists, histamine H₂ receptor antagonists, and/or glucocorticosteroids, 30 minutes to 2 hours prior to starting MONJUVI infusion to minimize infusion-related reactions.
R/R DLBCL=relapsed/refractory diffuse large B-cell lymphoma; ASCT=autologous stem cell transplant; CR=complete response rate; PR=partial response rate; DoR=duration of response; SD=stable disease.
L-MIND examined patients with a broad range of characteristics, including those considered difficult-to-treat1,3,4,5
- Primary refractory patients and those with an IPI score of 3 to 5 were enrolled; in separate analyses, these characteristics of high-risk DLBCL were linked to poor outcomes3,4†
Select baseline characteristics (N=71)1,5
| Time between first DLBCL diagnosis and first documented relapse or progression | |
|---|---|
| ≤12 months | 17 (23.9%) |
| >12 months | 53 (74.6%) |
| Unknown | 1 (1.4%) |
| IPI score at screening | |
| 0–2 (low and low-intermediate risk) | 34 (47.9%) |
| 3–5 (intermediate-high and high risk) | 37 (52.1%) |
| Prior therapies | |
| Primary refractory disease | 14 (19.7%) |
| Refractory to last prior therapy | 32 (45%) |
| Refractory to rituximab | 30 (42%) |
| Prior CD20-containing therapy | |
| 100% | |
| Median number of prior therapies | |
| 2 | |
| Prior lines of therapy | |
| 1 | 49% |
| 2 to 4 | 51% |
| Prior ASCT | |
| 9 (13%) | |
| Median age (range) | |
| 71 years (41-86 years) |
|
| Race‡ | |
| White | 95% |
| Asian | 3% |
| Sex, male | |
| 55% | |
| ECOG performance status | |
| 0 | 26 (36.6%) |
| 1 | 38 (53.5%) |
| 2 | 7 (9.9%) |
| Primary reasons patients were not candidates for ASCT | |
| Age | 47% |
| Refractory to salvage chemotherapy | 27% |
| Comorbidities | 13% |
| Refusal of high-dose chemotherapy/ASCT | 13% |
IPI=International Prognostic Index; ECOG=Eastern Cooperative Oncology Group.
†Based on a 2017 pooled data analysis from patients with refractory DLBCL in 2 observational cohorts and 2 large phase 3 randomized controlled trials (SCHOLAR-1) and a phase 2 trial of patients with stage II to IV newly diagnosed DLBCL and an IPI score of ≥3.
‡Race was collected in 92% of the 71 patients.
HIGH ORR REACHED, WITH A MAJORITY OF RESPONDERS ACHIEVING CR1
1-year primary analysis in patients with R/R DLBCL (N=71)1§
Hear Dr. Hayder Saeed of the Moffitt Cancer Center review the best overall response rate from L-MIND.
Play ORR VideoORR (3-year analysis)6
MONJUVI, in combination with lenalidomide, was granted accelerated approval based on the 1-year primary analysis of the L-MIND study. The data for the 3-year analysis of the L-MIND study has not yet been submitted to or reviewed by the FDA. The status with respect to potential inclusion of these data in the final, FDA-approved labeling has yet to be determined.
3-year follow-up analysis in patients with R/R DLBCL (N=71)6§
§Assessed by an Independent Review Committee.1,6
∥Due to rounding, ORR percentages may not correspond with the sum of CR and PR percentages.
The cutoff date for the primary analysis was November 30, 2018 and occurred after the last patient enrolled had completed 12 months of follow-up. The cutoff date for the 3-year follow-up analysis was October 30, 2020 and occurred after the last patient enrolled had completed 35 months of follow-up.6,7
Median time to response8
In the L-MIND study (n=71), the median time to response was 2.0 months
- Median time to CR: 10.9 months (n=25)
- Median time to PR: 1.9 months (n=26)
This analysis is exploratory in nature. These results should be interpreted with caution due to single-arm studies not adequately characterizing time-to-event endpoints, and the small sample size, which may lead to estimates that are unstable.
RESPONSE RATES IN 2L AND 3L+ IN PATIENTS WITH R/R DLBCL (3-YEAR ANALYSIS)6
MONJUVI, in combination with lenalidomide, was granted accelerated approval based on the 1-year primary analysis of the L-MIND study. The data for the 3-year analysis of the L-MIND study has not yet been submitted to or reviewed by the FDA. The status with respect to potential inclusion of these data in the final, FDA-approved labeling has yet to be determined.
3-year follow-up analysis in patients with R/R DLBCL (N=71)6¶
This analysis is exploratory in nature, and L-MIND was not designed or powered to evaluate and compare multiple subgroups.
These results should be interpreted with caution given the small sample size, which may lead to estimates that are unstable.
¶Assessed by an Independent Review Committee.6
#Due to rounding, ORR percentages may not correspond with the sum of CR and PR percentages.
The cutoff date for the primary analysis was November 30, 2018 and occurred after the last patient enrolled had completed 12 months of follow-up. The cutoff date for the 3-year follow-up analysis was October 30, 2020 and occurred after the last patient enrolled had completed 35 months of follow-up.6,7
L-MIND EXPLORATORY ANALYSIS: ORR BY SUBGROUP
(1-YEAR ANALYSIS)1,5
| Subgroup | Number of Patients | ORR (%) and 95% Cl |
|---|---|---|
| All patients (efficacy analysis) | 71 |
|
| Age | ||
| >70 years ≤70 years |
39 32 |
|
| IPI | ||
| Low risk and low-intermediate risk Intermediate-high and high risk |
34 37 |
|
| Cell of origin, phenotype |
||
| Non-GCB GCB Missing |
21 38 12 |
|
| Ann Arbor stage at baseline | ||
| I-II III-IV |
16 55 |
|
| Elevated LDH | ||
| Yes No |
40 31 |
|
| Rituximab refractory | ||
| Yes No |
30 40 |
|
| Refractory to last line | ||
| Yes No |
32 39 |
|
| Number of prior lines | ||
| 1 ≥2 |
35 36 |
|
| Prior autologous stem cell transplantation |
||
| Yes No |
9 62 |
|
| Sex | ||
| Female Male |
32 39 |
|
 |
This analysis is exploratory in nature, and L-MIND was not designed or powered to evaluate and compare multiple subgroups. These results should be interpreted with caution given the small sample size, which may lead to estimates that are unstable.
GCB=germinal center B-cell; LDH=lactate dehydrogenase.
SUSTAINED REMISSION IN PATIENTS WITH R/R DLBCL1
1-year primary analysis in patients with R/R DLBCL (N=71)1**††
Median DoR 21.7 months
(range: 0, 24)
(range: 0, 24)
Hear Dr. Hayder Saeed of the Moffitt Cancer Center review the duration of response data from L-MIND.
PLAY DoR VIDEOMedian DoR (3-year analysis)6
MONJUVI, in combination with lenalidomide, was granted accelerated approval based on the 1-year primary analysis of the L-MIND study. The data for the 3-year analysis of the L-MIND study has not yet been submitted to or reviewed by the FDA. The status with respect to potential inclusion of these data in the final, FDA-approved labeling has yet to be determined.
3-year follow-up analysis in patients with R/R DLBCL (N=71)6**††
NR=not reached.
**Assessed by an Independent Review Committee.1,6
††Kaplan-Meier estimates.1,6
The cutoff date for the primary analysis was November 30, 2018 and occurred after the last patient enrolled had completed 12 months of follow-up. The cutoff date for the 3-year follow-up analysis was October 30, 2020 and occurred after the last patient enrolled had completed 35 months of follow-up.6,7
DURATION OF RESPONSE BY PATIENT9
MONJUVI, in combination with lenalidomide, was granted accelerated approval based on the 1-year primary analysis of the L-MIND study. The data for the 3-year analysis of the L-MIND study has not yet been submitted to or reviewed by the FDA. The status with respect to potential inclusion of these data in the final, FDA-approved labeling has yet to be determined.
DoR by patient from time of initial response9
- The majority, or 63%, of responding patients (24/38) achieved a CR; nearly 50% (11/24) of those complete responses were observed at the first efficacy assessment (2 months)7,9
- About 40% (16/38) of the responding patients in the study converted from PR to CR (13/38), or had ongoing PR (3/38)—highlighting the importance of continuing treatment with MONJUVI and lenalidomide according to the dosage schedule9
This analysis is exploratory in nature. These results should be interpreted with caution due to single-arm studies not adequately characterizing time-to-event endpoints, and the small sample size, which may lead to estimates that are unstable.
This graph represents 38 out of the 71 patients in the L-MIND study who experienced a response; 33 patients did not experience a complete or partial response.
For patients whose response has stopped, events may include tumor progression, death, or beginning of a new anti-cancer treatment.
‡‡Two patients started a new anti-cancer treatment immediately after a response was recorded at the end of the treatment assessment.9
The initial assessment of efficacy/disease response was performed and recorded at Cycle 3, Day 1.7
The cutoff date for the primary analysis was November 30, 2018 and occurred after the last patient enrolled had completed 12 months of follow-up. The cutoff date for the 3-year follow-up analysis was October 30, 2020 and occurred after the last patient enrolled had completed 35 months of follow-up.6,7
REFERENCES: 1. MONJUVI Prescribing Information. Boston, MA: MorphoSys. 6/2021. 2. ClinicalTrials.gov. A study to evaluate the safety and efficacy of lenalidomide with MOR00208 in patients with R-R DLBCL (L-MIND). https://clinicaltrials.gov/ct2/show/NCT02399085?term=l-mind&draw=2&rank=1. Accessed January 17, 2022. 3. Crump M, Neelapu SS, Farooq U, et al. Outcomes in refractory diffuse large B-cell lymphoma: results from the international SCHOLAR-1 study. Blood. 2017;130(16):1800-1808. 4. McMillan AK, Phillips EH, Kirkwood AA, et al. Favourable outcomes for high-risk diffuse large B-cell lymphoma (IPI 3—5) treated with front-line R-CODOX-M/R-IVAC chemotherapy: results of a phase 2 UK NCRI trial. Ann Oncol. 2020;31(9):1251-1259. 5. Data on file. L-MIND primary analysis. MorphoSys. Boston, MA. 6. Data on file. 3-year follow-up analysis. MorphoSys. Boston, MA. 7. Data on file. CSR. MorphoSys. Boston, MA. 8. Data on file. Time to response tables. MorphoSys. Boston, MA. 9. Data on file. MOR208C203 (LMIND) - Medical Affairs Request Swimmer Plots USPI. MorphoSys. Boston, MA. 10. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for B-Cell Lymphomas V.3.2022. © National Comprehensive Cancer Network, Inc. 2022. All rights reserved. Accessed April 25, 2022. To view the most recent and complete version of the guideline, go online to NCCN.org.