Trial Outcomes & Findings for Pembrolizumab, Lenalidomide, and Dexamethasone in Treating Patients With Newly Diagnosed Multiple Myeloma Eligible for Stem Cell Transplant (NCT NCT02880228)

Last Updated: 2019-07-30

Results Overview

The International Myeloma Working Group response criteria was used to assess response to therapy. The proportion of VGPR response at any time during treatment with pembrolizumab added to lenalidomide and dexamethasone will be estimated by the number of patients achieving a VGPR, CR, or sCR at any time divided by the total number of evaluable patients. A very good partial response (VGPR) is defined as as a demonstration of: * Serum and urine M-component detectable by immunofixation but not on electrophoresis c or * greater than 90% reduction in serum m-component and urine m-component \<100 mg/24 h * If the only measurable disease is FLC, a ≥90% reduction in the difference between involved and involved FLC levels The proportion of successes will be estimated by the number of patients demonstrating a VGPR or better divided by the total number of evaluable patients. Confidence intervals for the true success proportion will be calculated according to the approach of Duffy and Santner.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

11 participants

Primary outcome timeframe

Up to 112 days

Results posted on

2019-07-30

Participant Flow

Participant milestones

Participant milestones
Measure	Treatment (Lenalidomide, Dexamethasone, Pembrolizumab) Patients receive 25 mg lenalidomide PO daily on days 1-21 and 40 mg dexamethasone PO daily on days 1, 8, 15, and 22. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also receive 200 mg pembrolizumab IV over 30 minutes on days 1 and 22 of course 1, day 15 of course 2, and day 8 of course 3. Courses 1-3 repeat beyond 3 courses in the absence of disease progression or unacceptable toxicity. Patients may undergo stem cell transplantation after 4 courses of treatment.
Overall Study STARTED	11
Overall Study COMPLETED	11
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Pembrolizumab, Lenalidomide, and Dexamethasone in Treating Patients With Newly Diagnosed Multiple Myeloma Eligible for Stem Cell Transplant

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Treatment (Lenalidomide, Dexamethasone, Pembrolizumab) n=11 Participants Patients receive 25 mg lenalidomide PO daily on days 1-21 and 40 mg dexamethasone PO daily on days 1, 8, 15, and 22. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also receive 200 mg pembrolizumab IV over 30 minutes on days 1 and 22 of course 1, day 15 of course 2, and day 8 of course 3. Courses 1-3 repeat beyond 3 courses in the absence of disease progression or unacceptable toxicity. Patients may undergo stem cell transplantation after 4 courses of treatment.
Age, Continuous	59 years n=5 Participants
Sex: Female, Male Female	4 Participants n=5 Participants
Sex: Female, Male Male	7 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	10 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants
Race (NIH/OMB) White	10 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants
Region of Enrollment United States	11 participants n=5 Participants

PRIMARY outcome

Timeframe: Up to 112 days

Outcome measures

Outcome measures
Measure	Treatment (Lenalidomide, Dexamethasone, Pembrolizumab) n=11 Participants Patients receive 25 mg lenalidomide PO daily on days 1-21 and 40 mg dexamethasone PO daily on days 1, 8, 15, and 22. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also receive 200 mg pembrolizumab IV over 30 minutes on days 1 and 22 of course 1, day 15 of course 2, and day 8 of course 3. Courses 1-3 repeat beyond 3 courses in the absence of disease progression or unacceptable toxicity. Patients may undergo stem cell transplantation after 4 courses of treatment.
Proportion of Complete Response Plus Very Good Partial Response (VGPR)	0 proportion of participants Interval 0.0 to 0.28

SECONDARY outcome

Timeframe: From registration to the earliest date of documentation of disease progression or death due to any cause, assessed up to 3 years

Population: All patients that began protocol treatment were included in this analysis.

Progression-free survival is defined as the time from registration to the earliest date of documentation of disease progression or death due to any cause. Patients who receive subsequent treatment for myeloma before disease progression will be censored on the date of their last disease assessment prior to initiation of the subsequent treatment. Transplant will not be considered subsequent treatment. The distribution of progression-free survival will be estimated using the method of Kaplan-Meier.

Outcome measures

Outcome measures
Measure	Treatment (Lenalidomide, Dexamethasone, Pembrolizumab) n=11 Participants Patients receive 25 mg lenalidomide PO daily on days 1-21 and 40 mg dexamethasone PO daily on days 1, 8, 15, and 22. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also receive 200 mg pembrolizumab IV over 30 minutes on days 1 and 22 of course 1, day 15 of course 2, and day 8 of course 3. Courses 1-3 repeat beyond 3 courses in the absence of disease progression or unacceptable toxicity. Patients may undergo stem cell transplantation after 4 courses of treatment.
Progression-free Survival	NA months Too few events occurred to estimate the median and confidence interval.

SECONDARY outcome

Timeframe: Up to 112 days

Population: Only patients that completed 4 cycles of treatment were included in this endpoint.

The PR response after 4 cycles of induction treatment with pembrolizumab added to lenalidomide and dexamethasone will be estimated by the number of patients who achieve a PR, VGPR, CR, or sCR after 4 cycles divided by the total number of evaluable patients. A PR is defined by the following criteria:\> * If present at baseline, ≥50% reduction of serum M-protein and reduction in 24-hour urinary M-protein or to \<200 mg/24hrs\> * If the only measurable disease is FLC, a ≥50% reduction in the difference between involved and involved FLC levels\> * If the only measurable disease is BM, a ≥50% reduction in BM PC's (provided the baseline PC's was ≥30%)\> * If present at baseline, ≥50% reduction in the size of soft tissue plasmacytomas\> Exact binomial 95% confidence intervals for the true success rate will be calculated.

Outcome measures

Outcome measures
Measure	Treatment (Lenalidomide, Dexamethasone, Pembrolizumab) n=5 Participants Patients receive 25 mg lenalidomide PO daily on days 1-21 and 40 mg dexamethasone PO daily on days 1, 8, 15, and 22. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also receive 200 mg pembrolizumab IV over 30 minutes on days 1 and 22 of course 1, day 15 of course 2, and day 8 of course 3. Courses 1-3 repeat beyond 3 courses in the absence of disease progression or unacceptable toxicity. Patients may undergo stem cell transplantation after 4 courses of treatment.
Partial Response (PR)	0 proportion of participants Interval 0.0 to 0.52

SECONDARY outcome

Timeframe: Up to 112 days

Population: Only patients that completed 4 cycles of treatment were eligible for this endpoint.

The proportion of successful stem cell collection following initial therapy with the combination of pembrolizumab, lenalidomide and dexamethasone in patients with newly diagnosed MM will be estimated by the number of patients with a successful stem cell collection divided by the total number of evaluable patients. Exact binomial 95% confidence intervals for the true successful proportion will be calculated.

Outcome measures

Outcome measures
Measure	Treatment (Lenalidomide, Dexamethasone, Pembrolizumab) n=5 Participants Patients receive 25 mg lenalidomide PO daily on days 1-21 and 40 mg dexamethasone PO daily on days 1, 8, 15, and 22. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also receive 200 mg pembrolizumab IV over 30 minutes on days 1 and 22 of course 1, day 15 of course 2, and day 8 of course 3. Courses 1-3 repeat beyond 3 courses in the absence of disease progression or unacceptable toxicity. Patients may undergo stem cell transplantation after 4 courses of treatment.
Proportion of Successful Stem Cell Collection	0.4 proportion of participants Interval 0.05 to 0.85

SECONDARY outcome

Timeframe: From time of registration to death due to any cause, assessed up to 3 years

Population: All patients that began protocol treatment are included in this analysis.

Survival time is defined as the time from registration to death due to any cause. The distribution of survival time will be estimated using the method of Kaplan-Meier.

Outcome measures

Outcome measures
Measure	Treatment (Lenalidomide, Dexamethasone, Pembrolizumab) n=11 Participants Patients receive 25 mg lenalidomide PO daily on days 1-21 and 40 mg dexamethasone PO daily on days 1, 8, 15, and 22. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also receive 200 mg pembrolizumab IV over 30 minutes on days 1 and 22 of course 1, day 15 of course 2, and day 8 of course 3. Courses 1-3 repeat beyond 3 courses in the absence of disease progression or unacceptable toxicity. Patients may undergo stem cell transplantation after 4 courses of treatment.
Survival Time	NA months Too few events occurred to estimate a median and confidence interval.

Adverse Events

Treatment (Lenalidomide, Dexamethasone, Pembrolizumab)

Serious events: 3 serious events

Other events: 11 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Treatment (Lenalidomide, Dexamethasone, Pembrolizumab) n=11 participants at risk Patients receive 25 mg lenalidomide PO daily on days 1-21 and 40 mg dexamethasone PO daily on days 1, 8, 15, and 22. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also receive 200 mg pembrolizumab IV over 30 minutes on days 1 and 22 of course 1, day 15 of course 2, and day 8 of course 3. Courses 1-3 repeat beyond 3 courses in the absence of disease progression or unacceptable toxicity. Patients may undergo stem cell transplantation after 4 courses of treatment.
Blood and lymphatic system disorders Anemia	9.1% 1/11 • Number of events 1 • Adverse events were collected after every 28 day cycles during treatment, up to 7 cycles.
Cardiac disorders Heart failure	9.1% 1/11 • Number of events 1 • Adverse events were collected after every 28 day cycles during treatment, up to 7 cycles.
General disorders Edema limbs	9.1% 1/11 • Number of events 1 • Adverse events were collected after every 28 day cycles during treatment, up to 7 cycles.
General disorders Fever	9.1% 1/11 • Number of events 1 • Adverse events were collected after every 28 day cycles during treatment, up to 7 cycles.
Infections and infestations Infections and infestations - Other, specify	9.1% 1/11 • Number of events 1 • Adverse events were collected after every 28 day cycles during treatment, up to 7 cycles.
Infections and infestations Sepsis	9.1% 1/11 • Number of events 1 • Adverse events were collected after every 28 day cycles during treatment, up to 7 cycles.
Investigations Neutrophil count decreased	9.1% 1/11 • Number of events 1 • Adverse events were collected after every 28 day cycles during treatment, up to 7 cycles.
Investigations Platelet count decreased	18.2% 2/11 • Number of events 2 • Adverse events were collected after every 28 day cycles during treatment, up to 7 cycles.
Investigations White blood cell decreased	9.1% 1/11 • Number of events 1 • Adverse events were collected after every 28 day cycles during treatment, up to 7 cycles.
Metabolism and nutrition disorders Hyperglycemia	9.1% 1/11 • Number of events 1 • Adverse events were collected after every 28 day cycles during treatment, up to 7 cycles.
Metabolism and nutrition disorders Hypocalcemia	9.1% 1/11 • Number of events 1 • Adverse events were collected after every 28 day cycles during treatment, up to 7 cycles.
Nervous system disorders Seizure	9.1% 1/11 • Number of events 1 • Adverse events were collected after every 28 day cycles during treatment, up to 7 cycles.
Reproductive system and breast disorders Reproductive system and breast disorders - Other, specify	9.1% 1/11 • Number of events 1 • Adverse events were collected after every 28 day cycles during treatment, up to 7 cycles.
Vascular disorders Hypertension	9.1% 1/11 • Number of events 1 • Adverse events were collected after every 28 day cycles during treatment, up to 7 cycles.

Other adverse events

Other adverse events
Measure	Treatment (Lenalidomide, Dexamethasone, Pembrolizumab) n=11 participants at risk Patients receive 25 mg lenalidomide PO daily on days 1-21 and 40 mg dexamethasone PO daily on days 1, 8, 15, and 22. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also receive 200 mg pembrolizumab IV over 30 minutes on days 1 and 22 of course 1, day 15 of course 2, and day 8 of course 3. Courses 1-3 repeat beyond 3 courses in the absence of disease progression or unacceptable toxicity. Patients may undergo stem cell transplantation after 4 courses of treatment.
Blood and lymphatic system disorders Anemia	81.8% 9/11 • Number of events 25 • Adverse events were collected after every 28 day cycles during treatment, up to 7 cycles.
Gastrointestinal disorders Constipation	36.4% 4/11 • Number of events 13 • Adverse events were collected after every 28 day cycles during treatment, up to 7 cycles.
Gastrointestinal disorders Diarrhea	27.3% 3/11 • Number of events 5 • Adverse events were collected after every 28 day cycles during treatment, up to 7 cycles.
Gastrointestinal disorders Nausea	18.2% 2/11 • Number of events 2 • Adverse events were collected after every 28 day cycles during treatment, up to 7 cycles.
Gastrointestinal disorders Vomiting	9.1% 1/11 • Number of events 1 • Adverse events were collected after every 28 day cycles during treatment, up to 7 cycles.
General disorders Fatigue	81.8% 9/11 • Number of events 27 • Adverse events were collected after every 28 day cycles during treatment, up to 7 cycles.
Investigations Creatinine increased	18.2% 2/11 • Number of events 2 • Adverse events were collected after every 28 day cycles during treatment, up to 7 cycles.
Investigations Hemoglobin increased	9.1% 1/11 • Number of events 1 • Adverse events were collected after every 28 day cycles during treatment, up to 7 cycles.
Investigations Neutrophil count decreased	36.4% 4/11 • Number of events 5 • Adverse events were collected after every 28 day cycles during treatment, up to 7 cycles.
Investigations Platelet count decreased	45.5% 5/11 • Number of events 9 • Adverse events were collected after every 28 day cycles during treatment, up to 7 cycles.
Investigations White blood cell decreased	45.5% 5/11 • Number of events 6 • Adverse events were collected after every 28 day cycles during treatment, up to 7 cycles.
Metabolism and nutrition disorders Hypokalemia	9.1% 1/11 • Number of events 1 • Adverse events were collected after every 28 day cycles during treatment, up to 7 cycles.
Skin and subcutaneous tissue disorders Rash maculo-papular	27.3% 3/11 • Number of events 4 • Adverse events were collected after every 28 day cycles during treatment, up to 7 cycles.

Additional Information

Shaji K Kumar MD

Mayo Clinic

Phone: 5072842511

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place