Nonsecretory Myeloma Research Articles

Nonsecretory Multiple Myeloma in a Seropositive Hepatitis B Patient with Thrombocytosis: A Case Report

Non-secretory Multiple Myeloma is a rare variant of multiple myeloma with similar clinical and radiological findings. It is characterized by the absence/lack of monoclonal M proteins in the serum and/or urine. An early diagnosis can help in alleviating its adverse outcomes. We report a case of a 56-year-old female presenting with generalized body weakness and swelling, pain in right lower chest and anorexia. The patient was a known case of hepatitis B, treated a month ago. There was an incidental finding of thrombocytosis. Serum biochemistry and protein electrophoresis showed no findings in favor of Multiple Myeloma. Bence Jones proteins were negative in the urine. X-ray revealed few lytic lesions on calvaria of the skull. Bone marrow biopsy helped in diagnosing the patient as a case of non-secretory type of multiple myeloma highlighting the important role of this modality in saving the life of a patient through early diagnosis.

IgD Subtype But Not IgM or Non-Secretory Is a Prognostic Marker for Poor Survival Following Autologous Hematopoietic Cell Transplantation in Multiple Myeloma. Results From the EBMT CALM (Collaboration to Collect Autologous Transplant Outcomes in Lymphomas and Myeloma) Study

BackgroundThe Collaboration to Collect Autologous Transplant Outcomes in Lymphoma and Myeloma (CALM) study has provided an opportunity to evaluate the real-world outcomes of patients with myeloma. The aim of this study was to compare the outcome according to the different subtypes of myeloma using CALM data. PatientsThis study compared overall survival (OS), progression-free survival (PFS), and complete remission (CR) and the impact of novel versus non-novel drug containing induction regimens prior to autologous hematopoietic cell transplantation (HCT) of 2802 patients with “usual” and “rare” myelomas. ResultsOur data suggest that IgM and non-secretory myeloma have superior PFS and OS compared with IgD myeloma and outcomes comparable to those for usual myeloma. Patients who received novel agent induction had higher rates of CR prior to transplant. Non-novel induction regimens were associated with inferior PFS but no difference in OS. Although not the primary focus of this study, we show that poor mobilization status is associated with reduced PFS and OS, but these differences disappear in multivariate analysis suggesting that poor mobilization status is a surrogate for other indicators of poor prognosis. ConclusionWe confirm that IgD myeloma is associated with the worst prognosis and inferior outcomes compared with the other isotypes.

Non-secretory multiple myeloma with unusual TFG-ALK fusion showed dramatic response to ALK inhibition

Non-secretory multiple myeloma (NSMM) constitutes a distinct entity of multiple myeloma characterized by the absence of detectable monoclonal protein and rarely an absence of free light chains in the serum and urine. Given its rarity, the genomic landscape, clinical course, and prognosis of NSSM are not well characterized. Here, we report a case of a patient with relapsed and refractory NSMM with brain metastasis harboring a TFG-ALK fusion showing a dramatic and durable (over two years) response to commercially available anaplastic lymphoma kinase (ALK) inhibitors. The case emphasizes the beneficial role of molecular profiling in this target-poor disease.

KarMMa-4: Idecabtagene Vicleucel (ide-cel, bb2121), a BCMA-Directed CAR T-Cell Therapy, in High-Risk Newly Diagnosed Multiple Myeloma

BACKGROUND: Despite the introduction of novel agents, patients with high-risk (Revised International Staging System [R-ISS] stage III) newly diagnosed multiple myeloma (NDMM) have a poor prognosis (median progression-free survival [PFS], 29 months), highlighting the need for novel disease-targeting approaches (Palumbo A, et al. J Clin Oncol. 2015;33:2863-2869). The BCMA-directed CAR T cell therapy ide-cel demonstrated deep, durable responses in heavily pretreated patients with relapsed and refractory MM (RRMM; Raje N, et al. N Engl J Med. 2019;380:1726-1737; Munshi NC, et al. J Clin Oncol. 2020;38[suppl] [abstract 8503]), including those with high-risk (R-ISS stage III) RRMM. Earlier use in this population-where there is potentially more bone marrow reserve, more healthy peripheral blood mononuclear cells, a less compromised immune status, and less extensive disease to debulk before cell therapy-may result in improved outcomes and offer an opportunity to replace transplant with CAR T cell therapy. KarMMa-4 is a multicenter, open-label, phase 1, single-arm study of ide-cel in patients with high-risk NDMM (R-ISS stage III disease per International Myeloma Working Group criteria). STUDY DESIGN: KarMMa-4 is enrolling patients with NDMM who have high-risk disease, defined as R-ISS stage III (ISS stage III [serum b2 microglobulin ≥ 5.5 mg/L] and cytogenetic abnormalities t(4;14), del(17p), and/or t(14;16) by interphase fluorescence in situ hybridization; or ISS stage III and serum lactate dehydrogenase > upper limit of normal). Patients must have received ≤ 3 cycles of the induction regimens listed below, be aged ≥ 18 years, and have Eastern Cooperative Oncology Group performance status 0-1. Patients with nonsecretory myeloma or central nervous system involvement are excluded. Patients can enroll between cycle 1 and cycle 3 of induction. Permitted induction regimens for cycle 1 are carfilzomib + lenalidomide + dexamethasone ± daratumumab (KRd ± DARA), lenalidomide + bortezomib + dexamethasone ± daratumumab (RVd ± DARA), or cyclophosphamide + bortezomib + dexamethasone (CyBorD). Induction regimens for cycles 2-4 are limited to KRd or RVd, with dexamethasone omitted during cycle 3. All patients will undergo leukapheresis for T cell collection after cycle 3, and ide-cel will be manufactured during cycle 4 of induction. Stem cell collection for future use may be conducted after cycle 3 (following leukapheresis) or cycle 4 (before lymphodepletion). Ide-cel is infused after 2 days of rest following lymphodepletion with 3 days of fludarabine 30 mg/m2 + cyclophosphamide 300 mg/m2. Lenalidomide-based maintenance may be provided upon bone marrow recovery or 90 days after ide-cel infusion, whichever is later. The primary endpoints are dose-limiting toxicity and safety. Secondary endpoints include complete response rate and overall response rate, duration of response, time to complete response, time to start of maintenance, feasibility of initiating maintenance, PFS, overall survival, and pharmacokinetics. Exploratory endpoints include safety of lenalidomide maintenance therapy, minimal residual disease, immunogenicity and biomarkers. The starting ide-cel target dose is 450 × 106 CAR+ T cells, with dose escalation/de-escalation (150, 300, and 800 × 106 CAR+ T cells). After identification of the optimal target dose, 12 patients will be enrolled in the dose-expansion phase. KarMMa-4 is registered at ClinicalTrials.gov: NCT04196491. Disclosures Usmani: Celgene: Other; Abbvie: Consultancy; Sanofi: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Honoraria, Other: Speaking Fees, Research Funding; Janssen: Consultancy, Honoraria, Other: Speaking Fees, Research Funding; SkylineDX: Consultancy, Research Funding; Seattle Genetics: Consultancy, Research Funding; Merck: Consultancy, Research Funding; Incyte: Research Funding; Pharmacyclics: Research Funding; Array Biopharma: Research Funding; GSK: Consultancy, Research Funding; BMS, Celgene: Consultancy, Honoraria, Other: Speaking Fees, Research Funding; Amgen: Consultancy, Honoraria, Other: Speaking Fees, Research Funding. Berdeja:Servier: Consultancy; Poseida: Research Funding; Lilly: Research Funding; Legend: Consultancy; Kite Pharma: Consultancy; Kesios: Research Funding; Karyopharm: Consultancy; Prothena: Consultancy; Acetylon: Research Funding; Amgen: Consultancy, Research Funding; Abbvie: Research Funding; Vivolux: Research Funding; Novartis: Research Funding; Bluebird: Research Funding; Bioclinica: Consultancy; BMS: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Cellularity: Research Funding; Constellation: Research Funding; CRISPR Therapeutics: Consultancy, Research Funding; CURIS: Research Funding; EMD Sorono: Research Funding; Genentech, Inc.: Research Funding; Janssen: Consultancy, Research Funding; Glenmark: Research Funding; Teva: Research Funding; Takeda: Consultancy, Research Funding. Truppel-Hartmann:bluebird bio, Inc: Current Employment, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); F. Hoffmann La Roche: Current equity holder in publicly-traded company, Ended employment in the past 24 months. Casadebaig:Bristol-Myers Squibb Company: Current Employment. Wortman-Vayn:Bristol-Myers Squibb Company: Current Employment. Shelat:Bristol-Myers Squibb Company: Current Employment. Novick:Bristol-Myers Squibb Company: Current Employment. Shah:GSK, Amgen, Indapta Therapeutics, Sanofi, BMS, CareDx, Kite, Karyopharm: Consultancy; BMS, Janssen, Bluebird Bio, Sutro Biopharma, Teneobio, Poseida, Nektar: Research Funding.

KarMMa-3: A Phase 3 Study of Idecabtagene Vicleucel (ide-cel, bb2121), a BCMA-Directed CAR T Cell Therapy Vs Standard Regimens in Relapsed and Refractory Multiple Myeloma

KarMMa-3: A Phase 3 Study of Idecabtagene Vicleucel (ide-cel, bb2121), a BCMA-Directed CAR T Cell Therapy Vs Standard Regimens in Relapsed and Refractory Multiple Myeloma

Pleural mass in a young male unfolding an uncommon presentation of multiple myeloma

Multiple myeloma is a malignant proliferation of the plasma cells and can be non-secretory in about 1 to 5 % cases. Pleura based mass lesions are uncommon in myeloma. Herein we report a case of non-secretory multiple myeloma presenting with a pleura based mass in a 40 year old male. Fine needle aspiration cytology with immunohistochemistry played a key role in the diagnosis of this case.

Clinical characteristics and outcomes of oligosecretory and non-secretory multiple myeloma.

Secretion of monoclonal immunoglobulins (MIg) detected in the serum and/or urine is one of the typical features of multiple myeloma (MM). However, some patients secrete MIg in quantities below "measurable" (termed oligosecretory MM) and others have no detectable MIgs by standard serum and urine immunofixation (termed non-secretory MM). In a cohort of 852 consecutive patients with active myeloma, we identified 100 (11.7%) patients with oligo/non-secretory MM, including 20 (2.3%) with non-secretory MM. Compared to patients with secretory MM, these were younger, less anemic, and had less often renal dysfunction and less extensive bone marrow infiltration. Presence and extent of bone disease were similar, however, hypercalcemia was less common and more often is ISS (International Staging System)-1 and, in those with available FISH (Fluoresense In Situ Hybridization), high-risk cytogenetics were less common. FLCs (Free Light Chains) were available in 17 patients with non-secretory MM: only 3 had normal FLC ratio; the others had abnormal ratio and 9/14 had involved FLC ≥ 100mg/L. The 4-year OS for patients with oligo/non-secretory disease was 64% vs 58% for secretory MM. In multivariate analysis, oligo/non-secretory disease was not an independent prognostic factor per se. Thus, 12% of MM patients present with oligo/non-secretory disease at diagnosis and have different biologic characteristics but similar outcome to other MM patients.

Outcome and characteristics of non-measurable myeloma: A cohort study with population-based data from the Swedish Myeloma Registry.

We describe survival in patients with oligo- and non-secretory multiple myeloma (MM). We refer to the whole group as non-measurable MM and compare it with secretory MM. Oligo-secretory MM was defined as M protein in serum <10g/L and M protein in urine <200 measured as mg/day, mg/liter or mg/mmol creatinine. If patients had no M protein, they were defined as non-secretory. The groups were also subdivided by Free Light Chains (SFLC) level and ratio. Out of 4325 patients with symptomatic MM in the Swedish Myeloma Registry during 2008-2016 eligible for the study, 389 patients (9%) had non-measurable MM. Out of these, 253 patients (6%) had oligo-secretory and 136 (3%) had non-secretory MM. Median survival for secretory MM was 42.7months, non-measurable MM 40.2months, oligo-secretory MM 38.6months, and non-secretory MM 44.6months. Difference in overall observed survival was non-significant for all groups when compared with secretory MM. Within non-secretory MM, stem cell transplantation (SCT), 95% being auto-SCT, was significant for superior survival in multivariate analysis (HR 0.048. P=.0015). In this population-based study, we found no difference in survival between oligo- or non-secretory MM when compared with secretory MM. SCT appears to be important also for patients with non-secretory disease.

Cold Agglutinin Disease in Non-Secretory Multiple Myeloma: A Case Report

Skin involvement is not common as the first manifestation of Multiple Myeloma (MM). Although extremely rare, leucocytoclastic vasculitis, plasmasytoma, autoimmune bullous disease, livedo reticularis and Raynaud’s phenomenon may be the initial presentation of MM. Raynaud’s phenomenon and livedo reticularis related to cold exposure can be due to Cold Agglutinin Disease (CAD) or cryoglobulinemia and can be seen as the first manifestation of MM. In this case study, we described a 55-year-old man complaining of limbs livedo reticularis and Raynaud’s phenomenon during cold weather. Further evaluations revealed anemia and elevated ESR. Skull X-ray showed multiple punched-out lesions. Finally, serum protein electrophoresis and bone marrow aspiration confirmed the diagnosis of non-secretory MM as the underlying disease of CAD. The patient was referred to the hematologist for the treatment of MM.

Health-related quality of life in multiple myeloma in Kurdistan Iraq

BACKGROUND: Health-related quality of life (HRQoL) in multiple myeloma (MM) gained increasing importance to ensure that the improved survival is associated with improved life quality.OBJECTIVES: The aim of this study was to assess the HRQoL in a cohort of myeloma patients from Kurdistan region in Iraq.MATERIALS AND METHODS: This observational, cross-sectional, multi-center study enrolled 138 patients with symptomatic MM patients. The patients' records were retrieved and they were also clinically assessed and appropriately investigated at the time of enrolment. HRQoL was assessed using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Multiple Myeloma module (EROTC QLQ-MY20.RESULTS: The 138 patients included had a mean age of 60.4 years and included 83 males and 55 females. Significant predictors of worse HRQoL disease symptoms and side effects of treatment domains included increasing age, female sex, and increase number of treatment courses. Other predictors associated with worse disease symptom domain include presence of bone lesions and nonsecretory myeloma versus light chain myeloma. Basic parameters including the concentration of monoclonal band, hemoglobin, serum creatinine, calcium, and albumin were not significant associated with scores in any of the domain while serum LDH was associated with worse side effects of treatment scores. Furthermore, it was noted that patients who had underwent autologous stem cell transplants had better HRQoL in all domains compared to other modalities of therapy, though this did not reach significance.CONCLUSIONS: HRQoL in MM treated in Iraqi Kurdistan is not much different from their Western counterparts and several predictors of worse QoL were identified in this cohort of patients.

Incidence and Outcomes of Extramedullary Myeloma in a South Australian Hospital

Introduction The overall incidence of extramedullary myeloma ranged from 6% to 30% 1-3 in reported literatures. The mechanism of extramedullary myeloma is poorly understood with some authors suggesting an increased incidence of extramedullary relapses post autologous or allogenic stem cell transplants 4. For our case series, we aim to compare the incidences, frequency of aberrant cytogenetic abnormalities and outcomes of extramedullary myeloma with current reported literature. Method We examined data from the myeloma database in the Royal Adelaide Hospital, South Australia, of patients presenting for treatment from June 2009 to June 2019. Patients with biopsy-proven extramedullary myelomas involving skin, organ or central nervous system, were selected. We looked at paraprotein subtype, cytogenetic abnormalities at diagnosis, sites of involvement, treatment details including autologous and allogenic stem cell transplants. Results A total of 743 patients presenting with myeloma from June 2009 to June 2019 were isolated. From these, a total of 47 (6%) patients with extramedullary disease were reported. Thirteen patients (3%) presented with extramedullary disease at diagnosis, while 34 patients (5%) presented with extramedullary disease at relapse. The most common involved paraprotein were IgG and IgA with an incidence of 38% each. Patients with excess lambda light chains (15%) formed the next most common subtype. Two patients had non-secretory myeloma. Majority of the patients (28%) did not have any cytogenetic abnormality as detected by conventional karyotype or FISH studies. The most common cytogenetic abnormality was +1q (15%), followed by hyperdiploidy (13%). Two patients did not undergo diagnostic bone marrow biopsies and 4 patients did not have cytogenetic and FISH analysis on their diagnostic bone marrow samples. The most common sites of EM disease are soft tissue plasmacytomas with an overall incidence of 46%; followed by major organ involvement at 31% and central nervous system involvement at 19%. Bortezomib-based therapy was the most common upfront treatment in 7 patients (54%) followed by immunomodulator (IMiD) based treatment with 4 patients (31%) being treated in this regime. A total of 7 patients underwent an autologous stem cell transplant with melphalan conditioning post induction therapy and 4 patients received maintenance therapy with an IMiD post transplant. Of the 13 patients who had extramedullary disease at diagnosis, 2 patients passed away due to progressive disease while 10 patients at this time of analysis are still alive. 1 patient was lost to follow up. Of the 47 patients with extramedullary disease, a total of 7 patients received an allogenic stem cell transplant as salvage therapy. Five patients received a salvage allogenic stem cell transplant and subsequently only had extramedullary disease manifestation post transplant. Of these patients, 2 patients passed away from progressive disease, 2 passed away of causes unrelated to disease, with one surviving patient. Of the remainder 2 patients, salvage allogenic stem cell transplant were only undertaken post diagnosis of relapsed extramedullary disease. Conclusions The overall incidence of extramedullary myeloma in our institution at 6% is slightly less than published case series in current literature 1-3. In this small case series, most patients did not have a cytogenetic abnormality detected at diagnosis while of the patients with cytogenetic abnormalities, the most common was +1q. This presents a different view with current literature suggesting high risk cytogenetic abnormalities such as del17p, del13q are more common in extramedullary myeloma 5,6. We did not routinely perform a bone marrow biopsy at relapse, nor were karyotype and FISH analysis analysed on biopsies from extramedullary sites. Extramedullary myeloma disease remains a heterogenous disease. Regardless of the presence of extramedullary disease, current Australian guidelines recommend induction therapy with a bortezomib-based therapy followed by high dose melphalan consolidation and autologous stem cell transplant in eligible patients. There are new novel agents available which may be used for treatment of relapsed disease however their efficacy in extramedullary disease is yet to be determined. Disclosures Yong: Celgene: Honoraria; Janssen: Other: other ; Amgen: Honoraria.

Real Life Use of Imaging in the Management of Newly Diagnosed Patients with Myeloma- Practical Perspectives from a UK Hospital

Background: The role of imaging in myeloma has gained increasing importance over the past few years. Cross‐sectional imaging techniques such as computed tomography (CT), magnetic resonance imaging (MRI) and 18fluoro‐deoxyglucose (18F‐FDG) positron emission tomography (PET/CT) have increased sensitivity of detection of myeloma bone lesions compared to skeletal plain radiographs. However, there is huge variation in practice both within the United Kingdom and internationally, as to the choice of modality due to differences in access to the techniques and the subtleties of the information gained from each type of imaging. At present whole body (WB) diffusion weighted (DW) MRI is not yet available in our hospital. Aim: To review compliance of our current practice with the 2017 British Society for Haematology (BSH) guideline "Use of imaging in the management of patients with myeloma". To review the number of imaging modalities performed in newly diagnosed myeloma patients. Audit Standard Criteria range: 100%, or if not achieved, there is documentation in the case notes that explains the variance. • Patient with suspected myeloma underwent whole body MRI (WB-MRI) or CT (unless excluded due to unsuitability of procedure for the patient). • Patient without established myeloma defining event (MDE) but with bone marrow plasma cells 10-60% and/or M-protein &gt;30g/l underwent WB-MRI, WB-CT or PET/CT. • WB/DW-MRI or PET/CT performed in the assessment of oligosecretory myeloma. • Whole spine MRI performed and reported within 24 hours of suspected cord compression in myeloma. • PET/CT or WB/DW-MRI performed in the diagnostic assessment of possible solitary plasmacytoma. Method: Data collection period was between 1st July 2017 to 30th June 2018. We included all adult patients (age at least18 years) who were newly diagnosed with myeloma or plasmacytoma in our Trust during the data collection period, and had their diagnostic imaging in our Trust.Data were retrospectively collected from multidisciplinary meeting lists, chemotherapy list, radiology department data and electronic patient record (EPR). Results: Forty patients were included in the audit, which included 31 myeloma patients, 8 smouldering myeloma patients, one plasmacytoma patient. There were no non-secretory or oligosecretory myeloma cases and there were no newly diagnosed myeloma patients presenting with suspected cord compression in our Trust during the data collection period. All patients (100%) with suspected myeloma underwent cross-sectional imaging at diagnosis. Twenty nine (73%) patients had low dose (LD) WB-CT, four (10%) had PET/CT and one (2%) had WB-MRI. Eleven (27%) had CT chest abdomen pelvis (CT-CAP) ; this latter group of patients came through the suspected cancer referral pathway. No skeletal surveys were performed for patients with newly diagnosed myeloma or plasmacytoma during the data collection period. All smouldering myeloma patients underwent LDWB-CT. All solitary plasmacytoma patients had PET/CT or WB/DW-MRI. Twenty out of 40 (50%) patients had more than one imaging modality. For the majority of these patients this comprised a CT and MRI whole spine/pelvis (40%) and 10% had a CT and PET-CT. Two patients had three modes of imaging. The main reasons for requesting MRI spine/pelvis were back pain, CT showed lytic lesion or mass in spine, CT showed equivocal lytic lesion or abnormal marrow signal in spine, CT showed no lytic lesion but clinically strongly suspected lytic lesion in spine. The main reasons for requesting PET/CT were CT showed equivocal lytic lesion, and suspected cancer. Conclusion: Our Trust has excellent compliance with the BSH guideline as all new myeloma patients underwent cross-sectional imaging with a CT. However, for half of these patients CT alone was inadequate to fully assess their bone disease, requiring an additional modality. Discussion: Patients with suspected myeloma are referred to the haematology department through different pathways, most commonly suspected myeloma and back pain (73%), and suspected cancer (27%). The route of referral often determines first imaging modality. For many patients more than one modality is required to accurately assess their bone disease, eg presence of focal lesions, active lesions, spinal cord compromise. This causes delay of making diagnosis and increased cost. Access to WB-DWI/MRI may address some if not all these issues. Disclosures No relevant conflicts of interest to declare.

Cytogenetic Features and Clinical Outcomes of Patients With Non-secretory Multiple Myeloma in the Era of Novel Agent Induction Therapy

BackgroundNon-secretory multiple myeloma (NSMM) is a rare subtype of multiple myeloma (MM) characterized by the absence of monoclonal protein in the serum and/or urine. We look at the clinical and cytogenetic features of NSMM in this study. Patients and MethodsThis study evaluates a cohort of 30 patients with newly diagnosed NSMM seen at the Mayo Clinic, Rochester, MN, between 2008 and 2018 and treated with novel agent induction therapies. Survival outcomes were estimated using the Kaplan-Meier method and compared using the log-rank test. ResultsThese patients with NSMM appear to have a large disease burden at diagnosis with a median bone marrow plasma cell percentage of 70% and more than one-half of all patients having Multiple Myeloma International Staging System Stage III disease. There was a higher preponderance for t(11;14) primary cytogenetic abnormality in this NSMM cohort, accounting for more than 50% of the cohort. Finally, the overall survival of this cohort appears to be slightly worse than a matched-control group of newly diagnosed patients with MM with secretory disease. ConclusionsFuture multi-institution studies confirming these above findings on this rare entity are warranted.

Nonsecretory Mutiple Myeloma. A Rare Hemathologic Entity and Possible Misdiagnosis. A Case Report Warning

Nonsecretory multiple myeloma (NSMM) is a rare subtype of mutiple myeloma (MM). MM is normally associated with the secretion of monoclonal Ig (M spike) detected by serum or urine immunofixation/ electrphoresis; however in NSMM an M spike is not dedected, thus leading to either a misdiagnosis or a delayed diagnosis. A recent method of assessment for plasma cell disorders, serum free light chain assay (SFLC), individuates cases with measurable amounts of FLC, i.e., oligosecretory multiple mieloma (OSMM) or FLC-MMs.

Petrous apex non-secretory plasma cell myeloma with aberrant cytokeratin expression

ABSTRACTMultiple myeloma is a monoclonal proliferation of plasma cells with common involvement of vertebrae, ribs and skull vault. However, involvement of skull base is relatively uncommon and myeloma manifesting initially as a petrous apex mass is distinctly rare. We report a rare case of non-secretory multiple myeloma in a 52-year-old Egyptian male presenting primarily as a right petrous apex mass with abducens nerve palsy. Additionally, neoplastic cells aberrantly expressed cytokeratin. Although rare, plasma cell myeloma should be considered in the differential diagnosis of petrous apex masses.

Usefulness of free light chain measurement in monoclonal gammopathy, other haematological malignancies and autoimmune diseases

Immunoglobulin light chains are called free when they are not linked with heavy chains to form a whole immunoglobulin. Quantification of free light chains is a part of the French national authority for health guidelines for diagnostic and follow-up of light chain, oligo or non-secretory myeloma and AL amyloidosis. Most recently, the World health organisation had included free light chains quantification in prognostic criteria for monoclonal gammopathy of undetermined significance. However the literature bring to light some other potential indications of this analysis in the exploration of monoclonal gammopathy, also in lymphoid malignancies and some autoimmune diseases such as diabetes, rheumatoid arthritis, systemic lupus erythematosus, multiple sclerosis and Sjögren syndrome.

Laboratory Features of Newly Diagnosed Multiple Myeloma Patients.

Objectives: Multiple myeloma (MM) is a malignant disorder characterized by proliferation of a single clone of plasma cells derived from β-cells in the bone marrow. It is the second most common adult hematological malignancy, and it is the most common cancer with skeletal components as its primary site. The purpose of the retrospective study was to assess the hematological profile, different biochemical parameters, and the serum electrophoresis patterns of patients consistent with clinical symptoms of multiple myeloma.Materials and methods: A retrospective study of 99 patients diagnosed with multiple myeloma (MM) was carried out at the Hematology Department of Benghazi Medical Center (BMC) in Benghazi, Libya from January 2010 to March 2017. Information on the laboratory features was obtained at presentation (before treatment) and analyzed.Results: Of the 99 study detected cases of multiple myeloma at diagnosis, 14% were younger than 45 years and 35% were 70 years or older. The mean age was 61 years, of which 42 (42.4%) were males and 57 (57.6%) were females. Anemia was seen in roughly half of the diagnosed cases, most of which was normocytic normochromic anemia. High erythrocyte sedimentation rate (ESR) was seen in 65.3% of cases and increased neutrophil-to-lymphocyte ratio (NLR) was seen in 29.7%. Other abnormal serum levels with regard to the cases are as follows: hyperproteinemia in 30%, low albumin/globulin (A/G) ratio in 54.2%, hypercalcemia in 11.3%, serum creatinine level of >2.0 mg/dL in 27.2% cases, and increased β2-microglobulin in 67%. Serum protein electrophoresis revealed a localized band in 70.8% of patients. Monoclonal bands were seen in 44 cases (95.7%) and a bi-clonal pattern in two cases (4.3%), 78% of M-band showed migration to γ-region of electrophoretogram and 18% to β-region.Hypogammaglobulinemia was detected in 32.8% and hypergammaglobulinemia was detected in 49.2%. Of the hypergammaglobulinemia, 18.1% showed polyclonal gammaglobulinemia. Bence Jones protein was positive in 50% cases. IgG was the commonest type, followed by IgA then light chain. In 26.5% of cases, the only diagnosis was multiple myeloma. Light chain multiple myeloma patients had high α2 globulin concentration and normal A/G ratio. Apart from the diagnosis of multiple myeloma, a number of cases had varying diagnoses including the following: 4% non-secretory myeloma, 2% amyloidosis with nephrotic syndrome, 2% liver cirrhosis, and 18.2% renal failure. Most patients presented in stage III.Conclusions: The presence of anemia, high ESR, and low A/G ratio in elderly patients should alert the clinician to investigate along the lines of multiple myeloma. In this study, unfortunately, the laboratory investigations were insufficient for diagnosing this disease in most patients. Most patients were diagnosed at stage III. Absence of paraprotein in the blood does not exclude multiple myeloma. It was further observed that most of the patients presented with significant renal damage, which attributed to hyperuricemia, hypercalcemia, or high NLR. Multiple causes of renal failure occur in myeloma and are often present at the time of diagnosis.

Clinical and cytogenetic features of nonsecretory multiple myeloma (NSMM) in the era of novel agent induction therapy: The Mayo Clinic experience.

e19519 Background: NSMM is a rare subtype of myeloma that has not been well characterized in the era of novel agent induction therapy. Thus, we evaluated the clinical and cytogenetic features of patients with newly diagnosed NSMM evaluated at our institution. Methods: We evaluated all NSMM patients seen at the Mayo Clinic, Rochester from 2008-2017 based on the absence of a detectable monoclonal protein in their serum and urine electrophoresis and having a concurrent involved serum immunoglobulin light chain of less than 5 mg/dL. Survival analysis was performed by the Kaplan-Meier method and clinical and cytogenetic features were reported descriptively. Results: This cohort consisted of 30 consecutive patients with NSMM with a median age of 62 years (40-79) of which 16 (53%) were male. The median bone marrow plasma cell involvement was 70% (Range: 0 – 100). There were 3/25 (12%) patients who presented with a creatinine of 2 mg/dL or greater and 6/23 (26%) patients who presented with hypercalcemia (11 mg/dL or greater). The ISS classification of this cohort is as follows: Stage 1- 8 (36%) patients, Stage 2- 3 (14%) patients and Stage 3- 11 (50%) patients. There were 6 (21%) out of 28 patients with high risk cytogenetics (either del 17p, t(4;14), t(14;16) or t(14;20). The distribution of primary cytogenetic abnormalities among this cohort was as follows: t(11;14) – 16 (57%), t(4;14) – 1 (4%), trisomies – 6 (21%) and other - 5 (13%). The median overall survival (OS) for patients in this cohort was 59 months (95% CI: 34 – 64). In comparison to a control cohort of newly diagnosed secretory myeloma patients matched for age, gender and year of diagnosis in a 1:2 ratio, the median OS was worse for the NSMM cohort but this was not statistically significant (59 vs. 92 months, p = 0.257). Conclusions: Patients diagnosed with NSMM had a predisposition towards having a t(11;14) primary cytogenetic abnormality. In the era of novel agent induction therapy, they may have a survival outcome that may be worse than newly diagnosed secretory myeloma patients.

Secretory status of monoclonal immunoglobulin is related to the outcome of patients with myeloma: a retrospective study

AbstractThe treatment of multiple myeloma (MM) with proteasome inhibitor (PI) bortezomib has significantly improved the survival of patients with MM. The 26S proteasome inhibitor targets the unfolded protein response (UPR) by inhibiting proteasome degradation of ubiquitinated paraprotein, subsequently leading to the lethal accumulation of paraprotein within the endoplasmic reticulum. According to secretory status of monoclonal immunoglobulin, newly diagnosed MM (NDMM) is divided into measurable and unmeasurable disease, which includes oligosecretory, nonsecretory, and nonproducer myeloma. The present study analyzed the clinical characteristics of 822 patients with NDMM who had either measurable or unmeasurable diseases and received bortezomib- or thalidomide-based therapies. Our results showed that the median progression-free survival (PFS) and overall survival (OS) of patients with MM was significantly longer in patients with measurable disease than those in oligosecretory, nonsecretory, and nonproducer MM (PFS: 27, 18, 19, and 2.0 months, respectively [P < .001]; OS: 51, 30, 22, and 2.0 months, respectively [P < .001]). Within the unmeasurable group, patients with nonproducer myeloma showed the shortest PFS and OS. Importantly, compared with thalidomide treatment, bortezomib significantly improved the PFS and OS of patients with MM with measurable disease (PFS: 25 and 33 months [P = .022], respectively; OS: 41 and 58 months [P < .001], respectively), but not those with unmeasurable disease (PFS: 18 and 16 months [P = .617], respectively; OS: 22 and 27 months [P = .743], respectively). Our results indicate that bortezomib-based therapy performed no better than thalidomide-based treatment in patients with unmeasurable MM. The results need to be confirmed in other patient cohorts, preferably in the context of a prospective trial.

Survival Outcomes of Young Multiple Myeloma Patients: A Single Center Experience

Multiple myeloma (MM) is a disease of the elderly. It shows rapidly increasing incidence with increased age. Although MM is rare in young people, patients diagnosed before the age of 50 years account for 10% of the overall incidence and approximately 2% are diagnosed before 40 years of age. The aim of the study was to assess the clinical results of the young MM patients diagnosed at the age of ≤45 years.All the MM patients who were ≤45 years old at the time of diagnosis and who were admitted to our clinic between January 2004 and December 2017 were retrospectively assessed. There was a total of 31 patients and 14 (45.2%) of them were females and 17 (54.8%) of them were males. The mean age was 40.4±3.8 years. The most frequent myeloma types were Ig G Kappa (n:12, 38.7%) and Kappa light chain (n: 10, 32.3%). The remaining types were Ig A lambda (n:4, 12.9%), Ig G lambda (n:2, 6.5%), Lambda light chain (n: 2, 6.5%) and non-secretory myeloma (n:1, 3.2%). Before transplantation 12 patients (38.7%) were in complete remission, 11 patients (35.5%) were in very good partial remission, 4 patients (12.9%) were in partial remission state and 4 patients (12.9%) had refractory disease. VAD + VCD protocol was given to 12 (38.7%) patients. 6 (19.8%) patients had VCD, 3 (9.7%) got VCD + VRD, 2 (6.5%) got VAD and 8 (25.8%) got other chemotherapy protocols. Transplantation was done in 26 patients (83.9%). Overall 9 patients (29%) died during the study period. Second or tandem transplantation was performed to 10 patients and 30% (n:3) of these re-transplanted patients died. The overall survival for these patients was estimated to be 70% (95% CI: 64.2-75.8).In conclusion MM in patients younger than 45 years is rare. In these patients Ig G Kappa and Kappa Light chain types are the most frequent types. Heterogeneous of individual patients may exist within these young myeloma patients. For those who are expected to show a poor response to current treatments despite their young age, the efficacy of an alternative therapeutic strategy such as front line allo-HSTC should be further investigated. DisclosuresNo relevant conflicts of interest to declare.