Multiple Myeloma

High risk MM:

• High risk cytogenetics: t(4;14), t(14;16), t(14;20), del 17p/monosomy17/TP53 mutation, 1q21 gain, MYC translocation, karyotype del 13

• R-ISS III

• Extramedullary disease

Standard risk MM:

• Favorable cytogenetics: t(6;14), t(11;14), Hyperdiploid karyotype

International Staging System:

Stage I:   B2 microglobulin <3.5 or Alb >3.5

Stage II:  Not stage I or III

Stage III: B2 microglobulin ≥5.5

Revised- International Staging System:

Stage I:   ISS stage I + no high-risk chromosomal abnormality AND normal LDH

Stage II:  Not stage I or III

Stage III: ISS stage III + high-risk chromosomal abnormality OR high LDH

Revised 2- International Staging System:

Low risk: 0 point

• Not stage II or III AND normal LDH AND no high risk chromosomal abnormality

Low intermediate: 0.5-1 points

• Stage II OR high LDH OR high risk chromosomal abnormality

High intermediate risk: 1.5-2.5 points 

• Any combination of high risk features which equals a score of 1.5-2.5

High risk: 3-5 points

• Any combination of high risk features which equals a score of 3-5

Medications:

Lenalidomide: 

• If CrCl >60: No adjustment

• If CrCl 30-60: 10-15 mg daily

• If CrCl <30: 15 mg every other day

• If patient is on HD: 5 mg daily

• Multiple myeloma and (Lenalidomide + Dexa): increases risk of thrombotic events → patients may need Aspirin or AC based on IMPEDE or SAVED scoring system. (You can search and memorize them or simply ignore them as I did)

Bortezomib:

• Does not need dose adjustment in renal failure

• Causes peripheral neuropathy

             - SQ causes less neuropathy compared to IV

• Particularly effective in patients with high risk chromosomal abnormalities

• If T.bili >1.5 xULN: dose  0.7 mg/m2 per injection

• Needs prophylaxis for shingles: Valacyclovir 500 mg po BID

Daratumumab:

• CD 38 antibody

Pomalidomide:

• For patients who:

• received at least one prior therapies including lenalidomide and Bortezomib

• disease progressed within 60 days after the last treatment

• Should not be given to patient if T.bili >2 and AST/ALT >3 xULN 

• Reduce the dose 25% in patients on HD

Ixazomib:

• For patients who received at least one prior therapies

• 46% improvement in PFS in patients with high risk cytogenetics

Elotuzumab:

• Targets SLAMF7 (on myeloma and NK cells)

Talquetamab:

• Targets CD3 and GPRC5D

Zoledronic acid:

• Side effects: myalgia, hypocalcemia, jaw osteonecrosis and renal failure

• Dose if:

- CrCl >60: 4.0 mg daily

- CrCl 50-60: 3.5 mg daily

- CrCl 40-50: 3.3 mg daily

- CrCl 30-40: 3.0 mg daily

- CrCl <30: Zoledronic acid is contraindicated

Denosumab:

• Can be offered to patients with kidney failure

Treatment regimens:

Non-transplant candidates:

• Lenalidomide + Dexa

• Lenalidomide + Dexa + Bortezomib (RVD) 

      - SWOG S0777 study: Adding Bortezomib to RD improves OS and PFS

• Lenalidomide + Dexa + Daratumumab 

      - MAIA study: Adding Daratumumab to RD improves PFS 

• Bortezomib + Melphalan + Prednisone (VMP)

Transplant eligible patients:

• RVD

• RVD + Daratumumab (GRIFFIN study)

• Carfilzomib + Lenalidomide + Dexa

• Avoid myelotoxic agents like Melphalan

Patients with myeloma kidney/renal failure:

• Cyclophosphamide + Bortezomib + Dexa (CyBorD) 

• These patients should not be treated with Lenalidomide initially. When the kidney function improves, treatment can be transitioned from CyBorD to RVD ± Daratumumab.

Refractory multiple myeloma (failed at least two prior treatments):

• Pomalidomide + Dexa

• Ixazomib + Lenalidomide + Dexa (TOURMALINE-MM1)

• Elotuzumab + Lenalidomide + Dexa 

• Elotuzumab + Pomalidomide + Dexa

Patients with significant neuropathy at baseline:

• Daratumumab

• Melphalan + Dexa (transplant ineligible)

Systemic Amyloidosis:

• CyBorD + Daratumumab and hyaluronidase 

• CyBorD

• Daratumumab

• Bortezomib + Melphalan + Dexa (transplant ineligible)