Early Stage Multiple Myeloma Research Articles

Erythropoietin Treatment in Advanced Multiple Myeloma Is Associated with Improved Immunological Functions: Could It Be Beneficial in Early Disease?.

Erythropoietin (Epo), the main growth regulator of erythropoiesis, is being used to treat anemias associated with renal disease and malignancies. We have previously observed prolonged survival of patients with advanced multiple myeloma (MM) who were treated with recombinant human Epo (rHuEpo) (Mittelman et al, Eur J Haematol 2004: 72:155). Further studies on murine MM models confirmed this observation and suggested that Epo has an anti-MM immunomodulatory effect (Mittelman et al. Proc Natl Acad Sci USA 2001: 98:5181; Katz et al. Acta Haematol 2005: 114:177). We have reported (ASH 2004) preliminary results showing that the rHuEpo-treated MM patients acquired improved immunological functions. We have since then extended the numbers of patients and the range of immunological functions tested. Here, we show that rHuEpo, prescribed for anemia in patients with advanced MM (Durie and Salmon Stage 2–3), is associated with effects on a variety of immunological parameters and functions, as presented in the table. Compared with non rHuEpo-treated MM patients, who demonstrated immunological abnormalities, rHuEpo-treated MM patients resumed normalization of the CD4:CD8 cell ratio, enhanced T-cell (both CD8 and CD4) PHA-mediated activation, improved mononuclear proliferation potential, higher expression of the co-stimulatory molecule CD28, lower values of the inhibitory CTLA-4 molecule and decreased levels of serum IL-6. The immunological parameters in the rHuEpo-treated MM patients were close to the normal healthy controls. Results are presented in the table below (mean +/− SE). We also found similar immunological abnormalities in patients at an early stage (Durie and Salmon stage 1, smoldering) MM (n=8).Our findings a) confirm and extend reports by others regarding immunological abnormalities in patients with advanced MM; b) show that patients with advanced MM treated with rHuEpo for their anemia benefit from improved immunological functions; c) show that patients with early-stage MM already manifest similar immunological abnormalities. Our data thus indicate that patients with early-stage MM might benefit from rHuEpo with improved immune functions, even prior to the development of anemia in later stages of the disease. Taken together, our study suggests rHuEpo as a potential immunomodulatory agent in the treatment of MM.ParameterNormal Healthy ControlsMM PatientsrHuEpo-treated Advanced MM PatientsEarly MMAdvanced MMNumber of PatientsN=14N=8N=21N=13CD4:CD82.4±0.31.2±0.2b1.2±0.1a1.9±0.3cPHA act- CD8+CD69+ (%)60±4.445±4.4b46.3±3a63.3±3.8cPHA act-CD4+CD69+ (%)57.1±3.842±4.6b43.3±3a59.9±3.6cProliferation (%)232.5±10.3161±7.1b146.5±15.1a218.1±22.5cCD8+CD28+ (%)73.2±5.253.7±8.238.8±2a55.6±2.9cCD8+CTLA-4+ (%)2.4±0.612.5±3.610.1±1.5a4.6±0.9csIL-6 (pg/ml)2.6±0.45.4±110±2.1a5.7±0.9ca. p<0.05 advanced MM compared to healthy controls. b. p<0.05 early MM compared to health controls. c. p<0.05 rHuEpo treated advanced MM compared to non-treated advanced MM patients

Zoledronic Acid Early Increases Serum Osteoprotegerin in Early Stage Multiple Myeloma.

Myeloma cells are able to induce an imbalance in the OPG/RANKL system in bone environment, and due to osteoclastic activation this is responsible for myeloma bone disease. Recent in vitro and in vivo evidence suggests that bisphosphonates exerts activity on myeloma cells, which could be of therapeutic interest particularly in patients in initial phases of multiple myeloma.We evaluated 26 patients with smoldering myeloma (stage IA) to assess basal levels of circulating cytokines as OPG, RANKL and macrophage inflammatory protein-1 alpha MIP-1α and serum markers of bone turnover at baseline and at 2, 4, 6 months and compared to 58 healthy subjects as control group. Moreover we treated 16 of those patients with a potent bisphosphonate, zoledronic acid (ZA), to find out if its antiosteoclastic activity can be related to changes in circulating levels of RANKL, OPG and (MIP-1α). Results showed serum levels of OPG significantly lower and an increase of RANKL:OPG ratio in MM patients respect to controls. A significant correlation was found between RANKL/OPG ratio and serum CTX (r=0.45;p<0.05). Patients with MM treated with zoledronic acid did not show significant changes in serum and urinary calcium as well as serum creatinine compared to untreated patients. An early and significant reduction of serum CTX was found in treated patients, while bone ALP decreased later and not significantly. Interestingly ZA increased serum OPG and reduced RANKL:OPG ratio (4,8±2,6 vs 2,9±0,8 ; p<0.05).The positive effect of zoledronic acid on bone tissue was confirmed by the increased in lumbar spine BMD at 6 months (+3.8%± 2.6 vs baseline; p<0.05). Larger studies are urgently needed to better clarify the significance of these findings.

CS1 Is Expressed on Myeloma Cells from Early Stage, Late Stage, and Drug-Treated Multiple Myeloma Patients, and Is Selectively Targeted by the HuLuc63 Antibody.

Introduction: One-third of multiple myeloma (MM) patients exhibit high-risk features such as abnormal cytogenetics, high LDH, amplification of CKS1-B or spiked expression of MAF, MAF-B or FGFR3. While not affecting complete response rates, median durations of event-free and overall survival, even with high-dose melphalan-based tandem autotransplants of such patients, do not exceed 24 mo and 36 mo, compared to 60 mo and ≥ 90 mo for the remainder. Monoclonal antibody (mAb)-mediated therapy may target a chemotherapy-resistant myeloma cell pool. CS1 (CD2 subset 1, CRACC, SLAMF7), a member of the CD2 family of cell surface glycoproteins, exhibits high-level expression on primary myeloma cells, indicating that CS1 is a potential target for treatment in MM.Methods: Gene expression was assessed using an Affymetrix GeneChip array. Protein expression was measured by flow cytometry, and immunohistochemistry (IHC), using HuLuc63, a novel humanized anti-CS1 mAb. HuLuc63-mediated lysis of myeloma cells via antibody dependent cellular cytotoxicity (ADCC) was measured by 51Cr-release.Results: CS1 mRNA was detected in >95% of CD138+ purified plasma cells from >95% of healthy donors, newly diagnosed myeloma patients, and those with relapsed myeloma (Fig. 1a). CS1 remained highly expressed in patients following VDTPACE treatment, albeit at a reduced level. CS1 expression was also high following bortezomib (Velcade®) treatment, with a subset of patients showing increased expression post-treatment. CS1 protein expression on primary myeloma cells was confirmed by flow cytometry, while IHC analysis of normal tissues revealed anti-CS1 staining primarily on CD138+ tissue plasma cells. Finally, we determined that HuLuc63 could induce killing of myeloma cells using purified allogeneic NK cells (Fig. 1b). Blocking the Fc receptor greatly reduced this activity indicating an ADCC mechanism. Killing of myeloma targets was also observed in autologous systems suggesting that HuLuc63 can overcome KIR-mediated NK cell inhibition of autologous NK cells. In summary, we observed high mRNA and protein expression of CS1 in myeloma from early stage, late stage, and treated patients, and showed enhanced lysis of myeloma cells in vitro with HuLuc63. Our data support the potential clinical utility of CS1-targeted therapy. HuLuc63 will be entering a phase I clinical trial for advanced myeloma patients. [Display omitted] [Display omitted]

Long-Term Results of Single-Agent Thalidomide as Initial Therapy for Asymptomatic (Smoldering or Indolent) Myeloma.

Background: Patients with early stage myeloma are typically observed without therapy until symptomatic disease occurs. We have reported early results of therapy with single-agent thalidomide as initial therapy for early stage multiple myeloma in an attempt to delay progression to symptomatic disease (Leukemia 2003; 17:775–9). We now report the long-term results of this phase II trial.Methods: Thirty-one patients with smoldering or indolent multiple myeloma were enrolled between April 1999–March 2002. All pts had bone marrow (BM) plasma cells >=10% and measurable disease defined as serum monoclonal (M) protein >=2gm/dL and/or urine M protein >=400mg/24 hours. Two patients were deemed ineligible because they were found to have received prior therapy for myeloma and were excluded from analysis. Thalidomide was initiated at a dose of 200 mg/day and increased as tolerated by 200 mg/day every 2 weeks to a maximum dose of 800 mg/day. The dose of thalidomide was decreased as needed to minimize toxicity. Treatment was continued until disease progression or serious toxicity, except for patients achieving less than a minor response (<25% paraprotein reduction) to therapy in whom therapy was stopped at one year. Response was defined as a decrease in serum and urine monoclonal (M) protein by 50% or higher. If the serum M protein was unmeasurable, a 90% or higher decrease in urine M protein was required. Responses need to be confirmed at least 4 weeks apart.Results: Ten patients (34%) had indolent myeloma, including 4 patients with lytic bone lesions, 3 patients with anemia (Hb <11gm/dL), and 3 patients with both anemia and lytic bone lesions. Median follow up of living patients is 5.6 years (range, 4.0–7.1 years). Of the twenty-nine eligible patients, ten (34%) had a partial response to therapy with at least 50% or greater reduction in serum and urine monoclonal (M) protein. Three patients are still on study and receiving therapy. The remaining have gone off-study: seven patients (27%)had progressive disease while on therapy; other reasons for ending study treatment included completed therapy per protocol (2 pts), patient refusal (2pts), toxicity (8 pts), alternate treatment (3 pts), other medical problems (1 pt), died on study (1 pt), and other (2 pts). The median time to progression (TTP) was 3.2 years (95% CI 2.1–5.6 yrs). Median progression free survival (PFS) was 3.0 yrs (95% CI 2.0–5.1 yrs). Median overall survival has not been reached; 5 year survival rate by the Kaplan Meier method is 60%. Major grade 3–4 non-hematologic adverse events at any time during therapy were noted in 34% of patients; this includes 14% with grade 4 toxicity. Grade 3–4 toxicities occurring in more than one patient include neuropathy (2 pts) and sinus bradycardia (2 pts).Conclusions: Thalidomide has activity in asymptomatic myeloma. This approach must be further tested in randomized trials to determine if the survival estimates are superior to observation. Given the activity of thalidomide, trials are also needed with lenalidomide.

Erythropoietin treatment in advanced multiple myeloma is associated with improved immunological functions: could it be beneficial in early disease?

Erythropoietin (Epo) is the main growth regulator of red blood cells, and recombinant human erythropoietin (rHuEpo) is thus used in clinical practice for the treatment of anaemia, primarily in kidney disease and cancer. rHuEpo treatment was found to be associated with prolonged survival of multiple myeloma (MM) patients. This clinical observation was then supported by studies on murine myeloma models. It thus appeared that rHuEpo had an anti-myeloma effect, causally related to an immunomodulatory function of rHuEpo. The present study investigated whether rHuEpo-treated MM patients acquire improved immunological functions. Treatment with rHuEpo, prescribed for anaemia that occurs in advanced disease, was associated with effects on a variety of immunological parameters and functions. This was expressed in an actual normalisation of the CD4:CD8 cell ratio, enhanced T cell phytohaemagglutinin-mediated activation and proliferation potential, T cell expression of the costimulatory CD28 and inhibitory CTLA-4 molecules, as well as reduced interleukin-6 serum values to normal levels. Furthermore, it was demonstrated that immunological abnormalities manifest in patients even in the early stages of MM. Our findings thus suggest that rHuEpo treatment might be effective in the early stages of MM, before anaemia develops. It is expected that this would boost the immune system, consequently achieving an anti-myeloma function; affecting disease progression and improving the prognosis.

Long-Term Id Vaccination Combined with IL-12 or IL-12 and GM-CSF in Early Stage Multiple Myeloma Patients.

The idiotypic structures expressed on the myeloma Ig protein may serve as tumor specific antigens and can be used as target structures for Id (Id) vaccination. In this study, 28 patients with IgG myeloma stage I-II were repeatedly immunized intracutaneously during a 110 week period with the autologous M-protein, either in combination with interleukin-12 (IL-12) (n=15), or with IL-12 and granulocyte-macrophage colony-stimulating factor (GM-CSF) (n=13). An Id-specific T cell response, as assessed by [3H]-thymidine incorporation, ELISPOT assay and delayed type hypersensitivity (DTH) reaction and strictly defined by 3 specified criteria, developed in 4/15 patients (27%) in the IL-12 group and 11/13 patients (85%) in the GM-CSF/IL-12 group (p=0.003). Three of 15 patients (20%) showed a gradually increasing Id-specific T cell response during the study whereas 10/15 patients (67%) showed an initial response which then disappeared rapidly; the latter pattern was frequently associated with subsequent progressive disease. In two patients (both in the IL-12 group) a reduction of the M-protein concentration by > 50% and >25%, respectively, was observed 18 and 21 months after the last immunization. These results indicate that Id immunization of myeloma patients using IL-12 and GM-CSF may more frequently induce a specific T cell response than with IL-12 alone, but also that repeated immunizations may result in a non-reversible state of tolerogenic T cells.

Three Cases of Synchronous Solid Tumor and Multiple Myeloma

The association between a multiple myeloma and a secondary solid tumor is not well established. Some reports showed an increased risk of secondary solid neoplasms in multiple myeloma patients, but others have not. Three cases of the synchronous occurrence of multiple myelomas and solid tumors, namely, a small cell carcinoma of the lung, an adenocarcinoma of the colon and a squamous carcinoma of the pyriform sinus were experienced at our hospital. Therefore, herein is reported the clinical courses and treatment results. The stage of multiple myeloma was Durie-Salmon stage I in all of three cases; therefore, the solid tumors were treated as a primary target because the prognosis of early stage multiple myeloma is generally better than that of advanced solid tumor, while a smoldering or stage I myeloma do not need primary therapy until progression of the multiple myeloma. Two patients died of their solid tumors, but one patient is alive.

Early versus deferred treatment for early stage multiple myeloma.

Early stage multiple myeloma (MM) represents about 20% of MM. Most of the patients are asymptomatic. Thus, it is far less dramatic than advanced disease and may require different treatment strategies. For these patients, it is not clear whether it is better to start chemotherapy right after the diagnosis or to delay the treatment until symptoms become obvious as the disease progresses. To identify and synthesize all available research evidence on whether early treatment intervention results in improved clinical outcomes when compared with observation alone. The main outcomes of interest that were examined included mortality, disease progression, response rate, and toxicity of early treatment. Searches of the following electronic databases were undertaken: MEDLINE, EMBASE, CANCERLIT, LILLIACS and Cochrane Database of RCTs. We have recently compiled a comprehensive database of RCTs in myeloma. This search was updated and supplemented by hand-search of abstracts from main society meetings such as the ASH (American Society of Hematology), ASCO (American Society of Clinical Oncology), and EHA (European Haematology Association). In addition, we compared our list with a list of RCTs maintained by the Oxford Clinical Trial Service Unit. Randomized controlled trials (RCT) with a parallel design that compared early versus deferred treatment of patients with early stage multiple myeloma based on Durie-Salmon (D-S) staging system. We also considered those trials that did not define early stage myeloma according to D-S staging system, but enrolled patients according to clinical uncertainty about the benefits of immediate intervention. Data synthesis was performed for all studies and according to the defined quality criteria. The first reviewer and the contact reviewer of this proposal independently extracted data. Disagreement was resolved by consensus. Revman software (ver 4.1) was used to combine results from all studies and expressed as an overall odds ratio or Peto's Odds Ratio, with 95% confidence interval. Three trials were included with a total of 131 patients in each of the early treatment and deferred treatment groups. Early MM is asymptomatic stage I in these trials. All trials used standard Melphalan treatment but not stem cell transplantation. No statistically significant heterogeneity among the studies was detected. Beneficial effects of early treatment were seen in delay of myeloma progression (Peto's OR = 0.16, 95% CI: 0.09-0.29), and reduced vertebral compression (OR = 0.18, 95%CI: 0.02-1.59, NNT = 23, 95% CI: an NNT of 11, via infinity, to an NNH of 50). No significant effects on mortality and response rate were seen (Peto's OR = 1.11, 95% CI: 0.67-1.84, and OR = 0.63, 95% CI: 0.33-1.23, respectively). Early treatment may increase the risk of acute leukemia (Peto's OR = 3.20, 95% CI: 0.55-18.73, NNH = 44, 95% CI: an NNT of 63, via infinity, to an NNH of 15). Early treatment of early stage multiple myeloma inhibits disease progression, and may reduce vertebral compression. However, early treatment may increase the risk of acute leukemia. However, the data on vertebral compression and leukaemic transformation may not be interpretable due to very small numbers. Based on the current evidence, mortality and response rate are not significantly affected by introducing early treatment in the progression of myeloma. However, it is quite possible that the lack of beneficial effects of early intervention in myeloma is a false negative result due to the paucity of the existing evidence. In addition, data on quality of life and toxicity were sparsely reported adding to additional difficulties about management decisions in early stage myeloma.

Idiotype Immunity (Natural and Vaccine-induced) in Early Stage Multiple Myeloma

Idiotypic structures expressed on the myeloma immunoglobulin (Ig) protein (M-component) might be regarded as tumor-specific antigens. Naturally occurring, idiotype-specific type I T-cell immunity has been observed preferentially in patients with early stage myeloma. The idiotypic structures on the clonal myeloma B-cells (B lymphocytes and plasma cells) may serve as targets for active immunization. Vaccination using the autologous monoclonal Ig as a vaccine has conferred resistance to tumor cell challenge in murine myeloma. The autologous myeloma Ig protein was used for immunization in patients with progressive stage I and early stage II multiple myeloma. When the idiotype (emulsified in aluminium phosphate) was used alone for immunization, a weak and transient idiotype-specific T-cell response was observed with no clinical effects. In our second series, the idiotype (in alum) was combined with GM-CSF. In all five patients, a specific T-cell response was induced consisting preferentially of MHC class I restricted (CD8 +) T-cells. Ig-specific CD4 + T-cells were also induced. A clinical response (> 50% reduction of the M-component concentration) was observed in one patient. These results indicate that idiotype-specific T-cell immunity may be induced or enhanced by idiotype Ig vaccination in patients with early stage multiple myeloma, in which the tumor load is relatively low and the immune system is functionally less compromized than in patients with chemotherapy-treated, advanced stages of the disease. The use of GM-CSF seems to be mandatory for the frequency and magnitude of the induced T-cell response. The optimal route, schedule and cytokine combination for idiotype immunization remains to be established.

The incidence of DNA aneuploidy in multiple myeloma does not correlate with stage of disease.

The bone marrow of 47 patients with multiple myeloma (MM), 2 patients with plasma cell leukemia, and 11 patients with monoclonal gammopathy of undetermined significance (MGUS) was analyzed by flow cytometry for the detection of DNA aneuploidy. The question to be addressed was whether a correlation exists between the incidence of DNA aneuploidy and the stage of disease. With one-parameter analysis of DNA staining, a DNA aneuploidy was detectable in 17 of 60 patients. The detection rate for DNA aneuploidies could be increased to 37 of 60 patients with the second method, the simultaneous measurement of DNA content in additional immunophenotyped cells (CD38 or B-B4). In MGUS and the early stages of MM, the discrepancy between both methods was higher than in stage III MM. There were no statistical differences in the incidence of DNA aneuploidy between MGUS or the early stages of MM and stage III MM (21/32 patients vs 16/26 patients). The CD56 expression in plasma cells was significantly higher in cases of DNA aneuploidy (mean +/- SD, 64.7% +/- 33.65% vs 39.3% +/- 36.69%; P = .028). Comparing the ratio of diploid to DNA aneuploid with that of CD56+ to CD56- plasma cells, a correlation was found in MGUS (r = 0.7320) in the early stages of MM, I and II (r = 0.8023), but not in stage III MM. Based on these data, the dual-staining method for DNA content in immunophenotyped cells is preferred for the detection of DNA aneuploidy, especially in the early stages of MM and in MGUS. The clinical importance of a classification of DNA aneuploidy and CD56 antigen expression together is proposed for testing.

Pediatric Solitary Plasmacytoma

Solitary plasmacytoma of bone (SPB) is a localized plasma cell neoplasm. SPB accounts for 5 10% of all plasma cell dyscrasias ( 1 -3). The relationship of SPB to multiple myeloma continues to be controversial. Many authors believe that SPB is an early stage of multiple myeloma ( I . 3-5). whereas others consider i t as a distinct clinical entity (6, 7). The occurrence of SPB in younger age groups and involvement of long bones is very rare. The youngest patient reported in the literature is 16 years old. Here we report a 15-year-old girl with SPB of the humerus with 10 yrars follow-up. She still remains in remission. Case report. A 15-year-old girl presented in March 1986 with a history of left shoulder joint pain of 6 months' duration. Pain appeared mainly on lifting the limb above the head. There was no history of any Trauma or swelling of the joint. On examination she was moderately built and nourished. There was no pallor or lymphadenopathy and no tenderness or swelling of the joint. Movements of the joint were full. A healed scar was seen over the anterior part of the left shoulder. Systemic examination did not reveal any abnormality. Suspecting a bone tumor open biopsy with curettage and bone grafting was performed in a peripheral hospital. She was later referred to us for further management. Investigations revealed Hb of 135 g/l. TLC of 7.5 x 109/1, platelets 300 x 109/l. and ESR 40 mm/lst hour. Urine analysis was normal. An x-ray of the shoulder joint showed osteolytic areas with ill-defined borders in the medial part of the head of the humerus (Figure). The biopsy showed mainly plasma cells in an amorphous background of which some were binucleate but the majority were mature. A few immature plasma cells were noted. In view of the plasma cell neoplasm she was investigated further for evidence of any systemic disease. However, skeletal survey, serum electrophoresis, immunoglobulin quantitation. bone marrow aspiration and biopsy were all normal. Bone scan showed a solitary lesion in the left humerus. In view of the isolated plasma cell tumor the diagnosis of solitary plasmacytoma of the bone was considered. She was treated with local radiotherapy-42 Gy in 14 fractions. The treatment was well tolerated. She has been followed up for the last 10 years and is still in remission. Discussion. Plasma cell neoplasma may be either localized (solitary plasmacytoma) or generalized (multiple myeloma). Solitary plasmacytoma may arise either in bone (solitary plasmacytoma of bone-SPB) or in extramedullary tissues. SPB accounts for 510% of patients with plasma cell neoplasm ( 1-3).

Tumour necrosis factor-alpha and interleukin 4 promote the differentiation of myeloma cell precursors in multiple myeloma.

The effects of tumour necrosis factor-alpha (TNF-alpha) and interleukin 4 (IL-4) on peripheral blood mononuclear cells (PBMC) from 36 patients with multiple myeloma (MM), 12 with monoclonal gammopathy of undetermined significance (MGUS) and 21 normal controls, were investigated. In 16/36 patients with MM, monoclonal plasma cells appeared after 4d in cultures containing TNF-alpha and IL-4. These changes were not observed in PBMC from patients with MGUS or from normal controls. These findings suggest that myeloma cell precursors do exist in the peripheral blood of MM patients and differentiate into plasma cells in the presence of TNF-alpha and IL-4. Based on these observations, we think that the variation in the number of myeloma cell precursors in peripheral blood could be used as a prognostic parameter of response to chemotherapy in myeloma patients. In addition, this assay may be useful to distinguish early-stage MM from MGUS.

Recruitment of new osteoblasts and osteoclasts is the earliest critical event in the pathogenesis of human multiple myeloma.

Considering the special relation of human multiple myeloma (MM) to bones, it is of importance to clarify the early steps of bone involvement in this disease. In this work, using bone histomorphometry (including histoenzymologic and kinetic studies for the first time), we have evaluated the bone remodeling (i.e., bone resorption and bone formation rates) of 16 individuals with early MM in comparison with that of 10 with benign monoclonal gammopathy (BMG) and that of 17 patients with previously untreated overt MM. A significantly increased osteoblastic recruitment was observed in the individuals with early MM when compared with those with BMG (P less than 0.01). A significant (P less than 0.01) increased bone resorption (i.e., eroded surfaces, osteoclast numbers and surfaces) was observed from the early stage of MM in comparison with the BMG status where bone resorption remained within the normal range. At the tissue level, there was no difference in terms of bone resorption between early and overt MM. On the other hand, osteoblast activity was significantly reduced in patients with overt MM (P less than 0.05 by comparison with those with early MM). A significant enhancement of osteoblastic recruitment with an increased generation of new osteoclasts is an early critical event in the pathogenesis of human MM. Of particular importance is the early stimulation of osteoblasts, since these cells produce high amounts of IL-6, a potent myeloma cell growth factor and a critical cytokine for the formation of osteoclasts in the bone marrow.

Treatment of Multiple Myeloma With Recombinant a-Interferon

Thirty-two patients with multiple myeloma were treated with recombinant alpha-interferon clone A (rIFN alpha A) daily by intramuscular injection with an initial dose of 12 X 10(6) U/m2. Of 27 patients evaluable for response, tumor responses were obtained in seven of 14 previously untreated patients (50%) and two of 13 who had relapsed or failed prior chemotherapy (15%). In all patients who had tumor response, there was restoration from subnormal levels of serum immunoglobulins, an effect infrequently observed with chemotherapy. The median duration of tumor responses exceeded 14 months (range, 6 to 20). Moderate-to-severe fatigue was the predominant side effect and necessitated dose reductions in all patients. We conclude that treatment of early stages of multiple myeloma with rIFN alpha A is beneficial because of the substantial response rate and the improvement in the synthesis of serum immunoglobulins. rIFN alpha A has a potential role in combination with other agents in the treatment of multiple myeloma.

Treatment of multiple myeloma with recombinant alpha-interferon

Thirty-two patients with multiple myeloma were treated with recombinant alpha-interferon clone A (rIFN alpha A) daily by intramuscular injection with an initial dose of 12 X 10(6) U/m2. Of 27 patients evaluable for response, tumor responses were obtained in seven of 14 previously untreated patients (50%) and two of 13 who had relapsed or failed prior chemotherapy (15%). In all patients who had tumor response, there was restoration from subnormal levels of serum immunoglobulins, an effect infrequently observed with chemotherapy. The median duration of tumor responses exceeded 14 months (range, 6 to 20). Moderate-to-severe fatigue was the predominant side effect and necessitated dose reductions in all patients. We conclude that treatment of early stages of multiple myeloma with rIFN alpha A is beneficial because of the substantial response rate and the improvement in the synthesis of serum immunoglobulins. rIFN alpha A has a potential role in combination with other agents in the treatment of multiple myeloma.

Rudimentary Paraproteinemia: Early Stage of Multiple Myeloma?

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