Transplantation eligible
Ref: Blood May 2022
10-15% of heme malignancies are myeloma
SOC- induction, high dose melphalan followed by aSCT, consolidation, then len maintenance
Why is transplantation under question? OS benefit has not been convincingly proved, even though PFS better with transplant in eligible patients.
Delayed ASCT can be done in younger individuals with standard risk disease if patient prefers due to social obligations. There is a risk of secondary primary malignancies. Updated IFM trial results report 8% secondary primary tumors over 8 yr and less than 2 percent AML, not different from non ASCT arm.
Choice of induction regimen: VRD ( PETHEMA/GEM 12, CR 33%) or D-VTD ( Cassiopeia tria)
D-VRD Griffin trial
Peripheral neuropathy rates: 9 percent ( D-VTD), 4 % VRD, D-VRD-7%
4-6 cycles of D-VRD or VRD followed by ASCT. After ASCT if standard risk__> len maintanance or consolidation followed by len maintenance
After ASCT, if high risk, tandem ASCT ( done within 6 months of ASCT -1) or VRD maintenance
In 2016, the International Myeloma Working Group (IMWG) made an attempt to find a consensus for the definition of HR cytogenetics MM,3 identifying patients with t(4;14), t(14;16), t(14;20), del17p, gain 1q, nonhyperdiploid karyotype, del13q at conventional karyotype, and HR signature at GEP as HR and all the others being standard risk
- t(4;14) FGFR3, MMSET
- t (4;16) cMAF
- t( 14;20)
- 1p32 unfavorable
- 1q gain if 4 or more, unfavorable
- Double hit- biallelic inactivation of TP53 ( very unfavorable)
- Single hit 17p
bortezomib-based treatments have improved, or even overcome, the poor prognosis imparted by t(4;14)
Discussion:
1. In designing a treatment plan, patient factors ( age, performance status and comorbidities) were taken into consideration. Additionally disease factors indicating disease burden ( beta 2 microglobulin, LDH, renal impairment, low albumin) and disease biology ( high risk GEP, cytogenetics, FISH) and organ dysfunction. He does not have > 20% circulating plasma cell or evidence of extramedullary disease both of which are suggestive of more aggressive disease.
2. We discussed the induction chemotherapy regimen RVD-Dara. We reviewed the side effects including but not limited to cytopenias, neuropathy, risk of blood clots, infusion reactions, need for blood transfusion support and rarely, death.
3. Anticoagulation risk mitigation:≤3 Points by IMPEDE Score or <2 Points by SAVED Score--> aspirin. Otherwise 10 mg xarelto or 2.5 mg BID apixaban.
4. Bone support: 2-3 yr Bisphosphonates. This can be administered q 3 months or q 4 weekly. In patients with significant bone disease or bone pain, q monthly for 1 y r can be considered. After discussing the options, we decided on q 3months. We reviewed the side effects including hypocalcemia, renal dysfunction and osteonecrosis of jaw among the most concerning se. Ocular toxicity is also associated with significant morbidity and the patient was advised to contact our office with any vision symptoms. I recommended a baseline dental exam and clearance by dentist as well as eye exam.
5. Hypercalcemia: bisphoshphonates as per #4.
6. Anemia: ESA not indicated. Correct nutritional deficiencies. Blood transfusion support per parameters.
7. ID prophylaxis: acyclovir
Rx of high risk disease:
Quadruplet induction (MoAb + PI + IMiD + dex)
Double ASCT
Quadruplet consolidation
Two-drug maintenance (PI + IMiD) for ≥2-3 y if sustained MRD−
Template:
Diagnosis: IgG kappa myeloma, RISS- stage
Transplantation eligibility
FISH
Cytogenetics
Date of diagnosis and initial presentation:
Presentation: details
CRAB
FLC
LDH
PET
BMBX:
Treatment history:
1. Date: RVD-dara
Date of progression
Comorbidities:diabetes mellitus, hypertension, heart failure, cardiac arrhythmias, hyperlipidemia, chronic renal failure, and other cancers
Geriatric/ frailty assessment:
End organ damage: renal failure, back pain, baseline neuropathy
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