Inclusion Criteria:
1. Age>18 years with no upper age limit. 2. Newly diagnosed multiple myeloma with indication for initiation of therapy.
3. ECOG performance status 0-2. 4. No prior MM-directed therapy except for dexamethasone (up to 160 mg) and/or bortezomib
(up to 5.2 mg/m2) and/or cyclophosphamide up to 1000 mg/m2 and/or lenalidomide (up to
21 days of therapy) administered for no longer than 4 weeks prior to enrollment (pre
induction). If subject received any prior therapy, pretreatment parameters necessary
for disease characterization and response assessment must be available.
5. Measurable disease meeting at least one of the following criteria (at screening or
prior to pre induction):
1. Serum monoclonal (M) protein ≥1.0 g/dl (≥0.5 g/dl if IgA, IgD, IgE or IgM
multiple myeloma)
2. ≥ 200 mg of M protein/24h in the urine. 3. Difference between affected and unaffected free light chain ≥10 mg/dL with
abnormal kappa to lambda ratio.
6. Have clinical laboratory values meeting the following criteria during the Screening
Phase and also at start of administration of study treatment. 1. Hemoglobin ≥7 g/dL (≥4.65 mmol/L; without prior RBC transfusion within 7 days
before the laboratory test; recombinant human erythropoietin use is permitted)
2. Platelets ≥75×10^9/L in participants in whom <50% of bone marrow nucleated cells
are plasma cells and ≥50×10^9/L in participants in whom.
- - 50% of bone marrow nucleated cells are plasma cells (without transfusion
support or thrombopoietin receptor agonist within 7 days before the
laboratory test)
3.
Absolute neutrophil count ≥1.0×109/L (prior growth factor support is permitted
but must be without support for 7 days for G-CSF or GM-CSF and for 14 days for
pegylated G CSF)
4. AST and ALT ≤2.5×ULN. 5. eGFR ≥30 mL/min based on Modified Diet in Renal Disease Formula calculation or
creatine clearance measured by a 24-hour urine collection. 6. Total bilirubin ≤2.0×ULN; except in participants with congenital bilirubinemia,
such as Gilbert syndrome (in which case direct bilirubin ≤1.5×ULN is required)
7. Serum calcium corrected for albumin ≤14 mg/dL (≤3.5 mmol/L) or free ionized
calcium ≤6.5 mg/dL (≤1.6 mmol/L)
7. A woman of childbearing potential must have a negative highly-sensitive serum
pregnancy test at screening and again within 24 hours of the start of study treatment
and must agree to further serum or urine pregnancy tests during the study. 8. A woman must be. 1. Not of childbearing potential, or. 2. Of childbearing potential and. 1. Practicing true abstinence; or. 2. Have a sole partner who is vasectomized; or. 3. Practicing ≥1 highly-effective, user-independent method of contraception. 9. A woman must agree not to donate eggs (ova, oocytes) or freeze for future use, for the
purposes of assisted reproduction during the study and for 90 days after receiving the
last dose of study treatment. 10. A man must wear a condom (with or without spermicidal foam/gel/film/cream/suppository)
when engaging in any activity that allows for passage of ejaculate to another person
during the study and for a minimum of 90 days after receiving the last dose of study
treatment. If a female partner is of childbearing potential, she must also be
practicing a highly effective method of contraception. 11. A male participant must agree not to donate sperm for the purpose of reproduction
during the study and for a minimum of 90 days after receiving the last dose of study
treatment.
12. Must be willing and able to adhere to the lifestyle restrictions specified in this
protocol. 13. Must sign an ICF (or their legally acceptable representative must sign) indicating
that the participant understands the purpose of, and procedures required for, the
study and is willing to participate in the study.
14. All participants must agree to comply with and be enrolled in Revlimid REMSTM program.
15. All participants must meet institution-specific criteria for AHCT eligibility as
assessed by the investigator.
16. In line with the higher incidence of MM in Blacks, and to address the historical
underrepresentation of ethnical minorities in MM trials, at least 25% of the enrolled
patients will be of ethnical minorities.
Exclusion Criteria:
1. Diagnosis of Plasma cell leukemia, primary light chain amyloidosis, POEMS, or
Waldenstrom's macroglobulinemia.
2. Contraindications or life-threatening allergies, hypersensitivity, or intolerance to
any study drug or its excipients (refer to the teclistamab Investigator's Brochure and
appropriate package inserts)
3. Prior or concurrent exposure to any of the following:
1. Teclistamab or any anti-BCMA therapy. 2. Daratumumab or any anti-CD38 therapy. 3. Targeted therapy, epigenetic therapy, or treatment with an investigational drug
or an invasive investigational medical device within 21 days or ≥5 half-lives,
whichever is less. 4. Investigational vaccine within 4 weeks. 5. Live, attenuated vaccine within 4 weeks before randomization.
6. Radiotherapy within 14 days or focal radiation within 7 days. 7. Gene-modified adoptive cell therapy (eg, chimeric antigen receptor modified T
cells, NK cells) within 3 months. 8. Cytotoxic therapy within 14 days. 9. PI therapy within 14 days. 10. IMiD agent therapy within 14 days. 4. Known active CNS involvement or exhibits clinical signs of meningeal involvement of
multiple myeloma. If either is suspected, negative whole brain MRI and lumbar cytology
are required.
5. Myelodysplastic syndrome or active malignancies (ie, progressing or requiring
treatment change in the last 24 months) other than multiple myeloma. The only allowed
exceptions are:
1. Non-muscle invasive bladder cancer treated within the last 24 months that is
considered completely cured. 2. Skin cancer (non-melanoma or melanoma) treated within the last 24 months that is
considered completely cured.
3. Noninvasive cervical cancer treated within the last 24 months that is considered
completely cured. 4. Localized prostate cancer (N0M0):
1. With a Gleason score of ≤6, treated within the last 24 months, or untreated
and under surveillance. 2. With a Gleason score of 3+4 that has been treated >6 months prior to full
study screening and considered to have a very low risk of recurrence, or. 5. History of localized prostate cancer and receiving androgen deprivation therapy
and considered to have a very low risk of recurrence.
6. Breast cancer: adequately treated lobular carcinoma in situ or ductal carcinoma
in situ, or history of localized breast cancer and receiving antihormonal agents
and considered to have a very low risk of recurrence. 7. Other malignancy that is considered cured with minimal risk of recurrence. 6. Stroke or seizure within 6 months prior to signing ICF.
7. Chronic obstructive pulmonary disease (COPD) with a forced expiratory volume in 1
second (FEV1) <50% of predicted normal. Note that FEV1 testing is required for
participants suspected of having COPD and participants must be excluded if FEV1 is
<50% of predicted normal.
8. Moderate or severe persistent asthma within the past 2 years or uncontrolled asthma of
any classification. Note that participants who currently have controlled intermittent
asthma or controlled mild persistent asthma are allowed to participate in the study.
9. Prior allogeneic bone marrow, hematopoietic stem cell or solid organ transplant.
10. Participant is pregnant, breast-feeding, or planning to become pregnant while enrolled
in this study or within 90 days after the last dose of study treatment.
11. Participant plans to father a child while enrolled in this study or within 90 days
after the last dose of study treatment.
12. Presence of the following cardiac conditions:
1. New York Heart Association stage III or IV congestive heart failure. 2. Myocardial infarction or coronary artery bypass graft ≤6 months prior to
randomization. 3. History of clinically significant ventricular arrhythmia or unexplained syncope,
not believed to be vasovagal in nature or due to dehydration. 4. History of severe non-ischemic cardiomyopathy. 13. Any of the following:
1. Known to be seropositive for human immunodeficiency virus. 2. Hepatitis B infection (ie, HBsAg or HBV-DNA positive). In the event the infection
status is unclear, quantitative viral levels are necessary to determine the
infection status.
3. Active hepatitis C infection as measured by positive HCV-RNA testing.
14. Major surgery within 2 weeks prior to the start of administration of study treatment,
or will not have fully recovered from surgery, or has major surgery planned during the
time the participant is expected to be treated in the study or within 2 weeks after
administration of the last dose of study treatment.
15. Significant neuropathy (Grades 3-4, or Grade 2 with pain) within 21 days prior to
registration.
16. Contra indication or intolerance to required supportive care medications.
17. Concurrent medical or psychiatric condition or disease that is likely to interfere
with study procedures or results, or that in the opinion of the investigator would
constitute a hazard for participating in this study, such as:
1. Uncontrolled diabetes. 2. Acute diffuse infiltrative pulmonary disease. 3. Evidence of active systemic viral, fungal, or bacterial infection, requiring
systemic antimicrobial therapy. 4. History of autoimmune disease with the exception of vitiligo, type I diabetes,
and prior autoimmune thyroiditis that is currently euthyroid based on clinical
symptoms and laboratory testing. 5. Disabling psychiatric conditions (eg, alcohol or drug abuse), severe dementia, or
altered mental status. 6. Any other issue that would impair the ability of the participant to receive or
tolerate the planned treatment at the investigational site, to understand
informed consent or any condition for which, in the opinion of the investigator,
participation would not be in the best interest of the participant (eg,
compromise the well-being) or that could prevent, limit, or confound the
protocol-specified assessments. 7. History of non-compliance with recommended medical treatments
