Ranjita Pallavi, MD
Patient Course at Bellevue
Patient presented with obstructive jaundice at an outside
hospital. ERCP was done and biopsy taken from ampulla of
vater mass was consistent with Plasmacytoma. Also
pancreatic mass was noted on CT but no biopsy could be
taken secondary to friability of the mass. Multiple myeloma
diagnosis was made based on SPEP, FLCA, Bone Marrow Exam
and Bone Survey and plan was to start on Bortezomib and
Lenalidomide which was changed to Bortezomib and
Cyclophosphamide secondary to renal failure. She got 2 cycles
and patient was then transferred to Metropolitan due to the
storm and off chemotherapy, with a prior diagnosis of sepsis.
• Multiple myeloma is a neoplastic plasma-cell disorder that is characterized by
clonal proliferation of malignant plasma cells in the bone marrow
microenvironment, monoclonal protein in the blood or urine, and associated
• It accounts for approximately 1% of neoplastic diseases and 13% of
• In Western countries, the annual age-adjusted incidence is 5.6 cases per
• It is estimated that 21,700 men and women (12,190 men and 9,510 women)
will be diagnosed with and 10,710 men and women will die of myeloma in
• Median age at diagnosis is approximately 70 years.
• In recent years, the introduction of autologous stem-cell transplantation and
the availability of agents such as thalidomide, lenalidomide, and bortezomib
have changed the management of myeloma and extended overall survival.
• In patients presenting at an age under 60 years, 10-year survival is
N Engl J Med 2011; 364:1046-1060 March 17,2011
Multistep Pathogenesis of Multiple Myeloma
N Engl J Med 2011; 364:1046-1060 March 17,2011
Diagnostic Criteria for Plasma-Cell
Disorder Disease deﬁnition
Monoclonal gammopathy of
All three criteria must be met Serum monoclonal protein <3 g/dL Clonal bone
marrow plasma cells <10%, and Absence of end-organ damage such as
hypercalcemia, renal insufﬁciency, anemia, and bone lesions (CRAB) that can
be attributed to the plasma cell-proliferative disorder; or in the case of IgM
MGUS no evidence of anemia, constitutional
symptoms, hyperviscosity, lymphadenopathy, or hepatosplenomegaly that
can be attributed to the underlying lymphoproliferative disorder
Smoldering multiple myeloma
(also referred to as
Both criteria must be met Serum monoclonal protein (IgG or IgA) 3 g/dL
and/or clonal bone marrow plasma cells 10% and Absence of end-organ
damage such as lytic bone lesions, anemia, hypercalcemia, or renal failure
that can be attributed to a plasma-cell proliferative disorder
All three criteria must be met Clonal bone marrow plasma cells 10% or biopsy
proven plasmacytoma Presence of serum and/or urinary monoclonal protein
(except in patients with true nonsecretory multiple myeloma) and Evidence
of end organ damage that can be attributed to the underlying plasma-cell
proliferative disorder, speciﬁcally Hypercalcemia: serum calcium 11.5 mg/dL
or Renal insufﬁciency: serum creatinine > 1.73 mmol/L (or >2 mg/dL) or
estimated creatinine clearance less than 40 mL/min Anemia: normochromic,
normocytic with a hemoglobin value of >2 g/dL below the lower limit of
normal or a hemoglobin value <10 g/dL
Bone lesions: lytic lesions, severe osteopenia, or pathologic fractures
• ~3% of plasma cell neoplasms
• Isolated plasma cell tumors of soft tissues
– Upper respiratory tract common, GI involvement
• Uninvolved marrow, negative skeletal survey
• M-protein present ~25% cases
– Disappears following treatment
• Curable with local radiation therapy
Autologous Hematopoietic Stem-Cell Transplantation for
Multiple Myeloma-Eligibility Criteria
• Recommended for patients with active myeloma who are relatively young and do not have
serious coexisting illnesses.
• In Europe, transplantation is generally considered only in patients 65 years of age or younger,
whereas in the United States, a formal age limit is not imposed.
• Free of significant renal dysfunction (usually with a creatinine level of <2.3 mg per deciliter
*203 μmol per liter+).
• Other coexisting illnesses of concern include serious cardiac, hepatic, neurologic, or
• Good functional status - (a performance status of less than grade 2, according to the Eastern
Cooperative Oncology Group scale)
June 18, 2009 Harousseau J.-L. and Moreau P.
N Engl J Med 2009; 360:2645-2654
Suggested Approach to the Treatment of Newly Diagnosed
n engl j med 364;11 nejm.org march 17, 2011
Cyclophosphamide, bortezomib and dexamethasone (CyBorD) induction for newly diagnosed
multiple myeloma: High response rates in a phase II clinical trial
• Mean 80% decline in the sentinel monoclonal protein at the end of two cycles.
• The overall intent to treat response rate (≥ partial response) was 88% with 61% ≥VGPR and
• For the 28 patients ( total 33) that completed all 4 cycles of therapy the CR/nCR rate was 46%
and ≥VGPR rate 71%.
• All patients undergoing stem cell harvest had a successful collection.
• Twenty three patients underwent SCT and are evaluable through day 100 with CR/nCR
documented in 70% and ≥VGPR in 74%.
• In conclusion, CyBorD produces a rapid and profound response in patients with newly
diagnosed multiple myeloma with manageable toxicity and adequate stem cells can be
collected from all patients using G-CSF alone or G-CSF plus cyclophosphamide allowing
patients to undergo SCT.
Leukemia. 2009 July; 23(7): 1337–1341.
MPR-R significantly prolonged progression-free survival in patients with newly
diagnosed multiple myeloma who were ineligible for transplantation, with the
greatest benefit observed in patients 65 to 75 years of age.
Salvage Therapy for Relapsed/Refractory Myeloma
A phase 2 study of single-agent carfilzomib (PX-171-003-A1) in patients with
relapsed and refractory multiple myeloma.
• 95% were refractory to their last therapy; 80% were refractory or intolerant to both bortezomib and
• Patients had median of 5 prior lines of therapy, including bortezomib, lenalidomide, and thalidomide.
• Overall response rate was 23.7% with median duration of response of 7.8 months.
• Median overall survival was 15.6 months.
• Common AEs were fatigue (49%), anemia (46%), nausea (45%), and thrombocytopenia (39%). Thirty-three
patients (12.4%) experienced peripheral neuropathy, primarily grades 1 or 2.
• Carfilzomib can be safely administered in patients with renal failure and adverse cytogenetics do not seem
to interfere with its activity.
Blood. 2012 Oct 4;120(14):2817-25. doi: 10.1182/blood-2012-05-425934. Epub 2012 Jul 25
Pomalidomide plus low-dose dexamethasone in myeloma refractory to both
bortezomib and lenalidomide: comparison of 2 dosing strategies in dual-refractory
Blood.2011 Sep 15;118(11):2970-5. Epub 2011 Jun 20