Meera Mohan

Inhibiting MEK in MAPK pathway-activated myeloma.

Over the last decade, new drugs have significantly changed the paradigm for treating multiple myeloma (MM), resulting in improved outcomes and reduced toxicity. However, many patients with MM relapse, and those who are refractory to or relapse after therapy with an immune-modulatory drug and a proteasome inhibitor have a dismal prognosis.1 Improving the outcome of relapsed and refractory MM is a significant clinical challenge. Importantly, in this respect, recently published data have established the frequent mutation of the RAS/mitogen-activated protein kinase (MAPK) pathway,2, 3, 4, 5 with mutations in NRAS, KRAS or BRAF being present in up to 50% of newly diagnosed MM cases. We routinely perform comprehensive genomic profiling using the FoundationOne Heme assay (Supplementary Methods). Review of these data shows the majority of the NRAS, KRAS and BRAF mutations occur in hotspots causing constitutive activation of the corresponding proteins. This makes the MAPK pathway a significant therapeutic target in MM.

Update on the optimal use of bortezomib in the treatment of multiple myeloma

The proteasome inhibitor (PI) “bortezomib” has now been in routine clinical practice for over a decade. It is now considered an important backbone therapy for all stages of the disease, and data continue to grow to support its use in newly diagnosed patients, relapsed and relapsed/refractory disease, maintenance therapy, high risk, and renal failure. Much has been learnt about the most clinically effective way of delivering therapy, with patients often benefiting more from a triplet bortezomib combination compared to a doublet combination. It is well tolerated and can be administered in the outpatient setting with manageable toxicity. The key to good results is managing side effects so that patients remain on therapy with minimal interruptions. Therefore, proactive management of peripheral neuropathy and thrombocytopenia is advised using dose delay and reduction strategies. The recent introduction of second- and third-generation PIs with different chemical and biological properties has resulted in a plethora of new clinical studies and has confirmed the ongoing role of this class of drugs in future myeloma therapy.

Gastrointestinal histoplasmosis in a patient after autologous stem cell transplant for multiple myeloma

A 59‐year‐old patient with multiple myeloma on maintenance chemotherapy presented with fever, weight loss, and night sweats. An F‐18 fluorodeoxyglucose (FDG) positron emission tomography (PET) computed tomography (CT) showed intra‐abdominal lymphadenopathy with a mesenteric mass that led to further workup and diagnosis of histoplamosis. The patient was treated with amphotericin B and subsequently switched to itraconazole. This exemplifies the usefulness of FDG PET CT in diagnosis of infectious complications.

The prognostic value of the depth of response in multiple myeloma depends on the time of assessment, risk status and molecular subtype

Complete remission (CR) rates for multiple myeloma (MM) have increased to 60% with current treatment approaches, including high dose melphalan-based autologous stem cell transplant (ASCT) and novel agents, and are associated with improved survival.[1][1]–[3][2] Despite this improvement, highly

Extensive Remineralization of Large Pelvic Lytic Lesions Following Total Therapy Treatment in Patients With Multiple Myeloma

Osteolytic bone lesions are a hallmark of multiple myeloma (MM) bone disease. Bone destruction is associated with severely imbalanced bone remodeling, secondary to increased osteoclastogenesis and significant osteoblast suppression. Lytic lesions of the pelvis are relatively common in MM patients and are known to contribute to the increased morbidity because of the high risk of fracture, which frequently demands extensive surgical intervention. After observing unexpected radiological improvement in serial large pelvic CT assessment in a patient treated in a total therapy protocol, the radiographic changes of pelvic osteolytic lesions by PET/CT scanning in patients who received Total Therapy 4 (TT4) treatment for myeloma were retrospectively analyzed. Sixty‐two (62) patients with lytic pelvic lesions >1 cm in diameter were identified at baseline PET/CT scanning. Follow‐up CT studies showed that 27 of 62 patients (43%) with large baseline pelvic lesions achieved significant reaccumulation of radiodense mineralization at the lytic cortical site. The average size of lytic lesions in which remineralization occurred was 4 cm (range, 1.3 to 10 cm). This study clearly demonstrates that mineral deposition in large pelvic lesions occurs in a significant proportion of MM patients treated with TT4, potentially affecting patient outcomes, quality of life, and future treatment strategies.

Lasiodiplodia species fungal osteomyelitis in a multiple myeloma patient.

Lasiodiplodia species are environmental fungi that have been reported as a cause of infection in both immunocompetent and immunocompromised patients. We present a case of fungal osteomyelitis caused by Lasiodiplodia species in a patient with multiple myeloma after autologous stem cell transplant. The patient was successfully treated with a combination of surgery and oral voriconzole. To the best of our knowledge, this is the first reported case of fungal osteomyelitis caused by Lasiodiplodia species.

A Case of Cardiac Light Chain Deposition Disease in a Patient with Solitary Plasmacytoma

Patient: Male, 31 Final Diagnosis: Light chain depsotion disease Symptoms: — Medication: — Clinical Procedure: None Specialty: Hematology Objective: Rare co-existance of disease or pathology Background: Light chain deposition disease is a systemic disease characterized by deposition of immunoglobin light chains in various organs. Cardiac involvement of light chain deposition disease, also known as cardiac nonamyloidotic immunoglobin deposition disease (CIDD), is a rare clinical entity, where clinical outcome is very variable and best treatment approaches are not well known. Case Report: We present the case of a 31-year-old man with a solitary thoracic plasmacytoma and cardiac light chain deposition disease with evidence of congestive heart failure by echocardiography and cardiac markers. The patient underwent surgical resection of the plasmacytoma followed by systemic therapy with 50% VDT-PACE and then VRD with near-normalization of his heart function. A melphalan-based stem cell transplant is planned in this young patient to achieve the best possible long-term remission. Conclusions: CIDD is a very rare disease, with previous reports showing diverse manifestations with variable outcome. A high level of clinical suspicion should be maintained in such cases and early intervention, as in our patient, can restore cardiac function. There is very little literature on the optimal management of these patients. A combination of surgery and chemotherapy were pursued in our patient with very good results.

Effect of low-dose bortezomib on bone formation in smouldering multiple myeloma

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Clinical characteristics and prognostic factors in multiple myeloma patients with light chain deposition disease

Light chain deposition disease (LCDD) is characterized by monotypic immunoglobulin depositions which will eventually lead to loss of organ function if left untreated. While the kidney is almost always affected, the presence and degree of LCDD in other organs vary. Ten to thirty percent of LCDD patients have underlying Multiple Myeloma (MM), yet outcome and prognostic markers in this particular patient group are still lacking. Here, we analyzed 69 patients with MM and biopsy proven LCDD and report on renal and extra‐renal involvement and its impact on prognosis as well as renal response depending on hematologic response. Coexisting light chain diseases such as AL amyloid and cast nephropathy were found in 30% of patients; those with LCDD and concurrent amyloid tended to have shorter survival. Cardiac involvement by LCDD was seen in one‐third of our patients and was associated with shorter overall survival; such patients also had a significantly higher risk of treatment‐related mortality (TRM) after stem cell transplant (SCT) compared to LCDD patients without cardiac involvement. This study highlights that MM patients with LCDD present with different clinical features compared to previously reported LCDD cohorts. Rapid initiation of treatment is necessary to prevent progressive renal disease and worse outcome. Coexisting light chain diseases and cardiac involvement are more common than previously reported and confer worse clinical outcome, emphasizing the need for careful patient careful patient evaluation and treatment selection.