Interferon Maintenance Therapy Research Articles

Maintenance therapy for chronic hepatitis C

Major progress has been made in the treatment of chronic hepatitis C virus (HCV) infection over the 18 years since Hoofnagle et al. initially documented response of non-A non-B hepatitis to interferon alfa. Current optimal therapy with pegylated interferon alfa (PEG-IFN) and ribavirin results in sustained virologic response rates of just over 50%. With an estimated 2.7 million Americans with active HCV infection, we can anticipate a large number of potential treatment failures with the current standard of care. At this time, no therapy is approved by the US Food and Drug Administration for treatment failures of PEG-IFN and ribavirin. Maintenance interferon therapy with the goal of prevention of disease progression rather than viral eradication appears to offer an option for HCV treatment failures with advanced disease. Alternative medical strategies to reduce hepatic fibrosis are also under investigation. With the relatively static number of available organs for transplantation, prevention of disease progression and decompensation is essential for an impact to be made upon the predicted rates of HCV morbidity and mortality in the next 10 to 20 years.

Mantle Cell Lymphoma: At Last, Some Hope for Successful Innovative Treatment Strategies

While it is quite unusual for totally new types of cancer to develop, it is not unusual for new and distinct forms of cancer to be recognized among what were previously thought to be well-defined homogeneous diseases. Such is the case with mantle cell lymphoma (MCL). Originally recognized in Europe and subsequently called many different names, the unifying term MCL was proposed by an international consensus conference in 1992. Morphology alone was not sufficient to accurately separate these cases from other “small round cell” lymphomas. However, morphology plus an immunophenotype consisting of CD20 , CD22 , IgM , IgD , and CD5 , as well as either detection of the characteristic chromosomal translocation t(11;14) or overexpression of the resultant gene product cyclin D1, result in an accurate diagnosis. Furthermore, the previously unrecognized entity of MCL was not rare and actually represented 6% of all non-Hodgkin’s lymphomas. A retrospective review of 375 patients enrolled on Southwest Oncology Group (SWOG) indolent lymphoma clinical trials demonstrated that these cases did not have an indolent course: the median progression-free survival following initial treatment was only 20 months, the median survival was only 36 months, and no patients were cured of their disease. A subsequent review of 524 patients treated on 12 different clinical trials revealed amazing uniformity in the treatment results. Thus, in comparison with the indolent lymphomas, which were incurable but had a median survival of 7 to 10 years, and the aggressive lymphomas, which could be cured in 40% to 50% of all cases, patients with MCL could be viewed as havingtheworstprognosisofallformsoflymphoma.ThatmanuscriptconcludedthatpatientswithMCL“arecandidatesforinnovative (and hopefully more successful) therapy.” Clinical trials conducted in the intervening years have generally yielded disappointing results. Although there is no established standard of care for patients with MCL, combination chemotherapy with CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) remained the most commonly used initial treatment, especially in the United States. There still remains some controversy over the value of doxorubicin. Fludarabine-based regimens are also utilized. After rituximab was shown to have an approximately 30% response rate in patients with relapsed MCL, Howard et al conducted a phase II study of CHOP plus rituximab (RCHOP) in untreated patients. Although they did note an increased complete remission rate compared with historical controls, there did not seem to be any difference in progression-free or overall survival. Hiddeman et al recently reported the initial results of a relatively small randomized trial in untreated MCL comparing CHOP and R-CHOP. Although there seemed to be some improvement in time to treatment failure from the addition of rituximab, the magnitude of the benefit was not great. The study also had a second randomization to interferon maintenance therapy or autologous stemcell transplantation; those aspects of the study have not yet been analyzed. The only published trial that reported greatly improved results in MCL was a single-institution study by The M.D. Anderson Cancer Center group, with relatively short follow-up, utilizing HyperCVAD (fractionated cyclophosphamide, doxorubicin, vincristine, dexamethasone) with or without stem-cell transplantation. However, allogeneic transplantation is not an option for most patients with MCL because of their median age of 60 years; the vast majority of patients who undergo autologous stem-cell transplantation will relapse. Subsequently, the same group reported that the addition of rituximab to the HyperCVAD regimen eliminated the need for stem-cell transplantation. A national phase II trial of that same regimen is currently being conducted by SWOG. Thus, it is clear that new therapeutic approaches for the treatment of patients with MCL need to be developed. A series of new agents, including bortezomib, thalidomide, flavopiridol, pixantrone, m-TOR inhibitors, and others, has shown some initial activity in pretreated patients. In this issue of the Journal, O’Connor et al and Goy et al, report the results of JOURNAL OF CLINICAL ONCOLOGY E D I T O R I A L VOLUME 23 NUMBER 4 FEBRUARY 1 2005

Evolution of the HALT-C Trial: pegylated interferon as maintenance therapy for chronic hepatitis C in previous interferon nonresponders

The Hepatitis C Antiviral Long-term Treatment against Cirrhosis (HALT-C) Trial was designed to determine whether maintenance interferon therapy could slow disease progression in patients who had failed to eradicate hepatitis C virus (HCV) during prior interferon treatment (nonresponders). Ten clinical sites, a virological testing center, and a data coordinating center (DCC) were selected to collaborate in the design and implementation of the final protocol. Eligible patients had been treated previously with interferon for at least 12 weeks, with or without another antiviral, ribavirin, but still had persistent viremia. Because patients had received a variety of prior treatments, and as a perceived benefit of enrollment, we incorporated a Lead-in period of treatment with long-acting pegylated interferon alfa-2a plus ribavirin into the study design, a combination believed to be more effective but not approved by the Food and Drug Administration at the Trial's inception. If patients failed to achieve clearance of virus from the blood after 20 weeks of this Lead-in therapy, they were entered into the main trial at week 24 and randomized to receive either a lower dose of pegylated interferon weekly alone or no further therapy for an additional 3 1/2 years. The original protocol was amended later in three respects to improve enrollment and to adapt to Food and Drug Administration approval of the Lead-in therapy, including allowing patients to proceed directly to the randomized part of the study if treatment resembling the Lead-in had been completed. The protocol changes enhanced enrollment while upholding the original goals of the study and its integrity.

Fludarabine, mitoxantrone, dexamethasone (FND) compared with an alternating triple therapy (ATT) regimen in patients with stage IV indolent lymphoma

Treatment for patients with stage IV indolent lymphoma ranges from watchful waiting to intensive chemotherapy and stem cell transplantation. In this trial we compared 2 induction regimens followed by 1 year of interferon maintenance therapy. Fludarabine, mitoxantrone (Novantrone), and dexamethasone (FND) were compared with an alternating triple therapy (ATT) regimen (CHOD-Bleo, ESHAP, and NOPP). Maintenance interferon/dexamethasone was given for 1 year in both treatment arms. Endpoints were comparisons of remission rates, survival, failure-free survival (FFS), molecular response rates, and toxicities. One hundred forty-two patients with previously untreated stage IV indolent lymphoma were evaluable (73 on FND; 69 on ATT). The overall response rates were 97% for FND and 97% for ATT (P =.9). The median follow-up is 5.9 years. The 5-year survival rates were 84% with FND and 82% with ATT (P =.9); the 5-year FFS rates were 41% with FND and 50% with ATT (P =.02). In a multivariate analysis, factors predicting for longer FFS were beta(2)-microglobulin less than 3 mg/L (P =.01) and ATT treatment (P =.03). ATT was associated with a substantially higher rate of grade 3-4 toxicities than FND. In conclusion, both regimens were associated with high rates of response and survival. ATT was associated with substantially longer FFS, but it was more toxic than FND.

Efficacy of Fludarabine/Mitoxantrone/Dexamethasone Alternating with CHOP in Bulky Follicular Non-Hodgkin's Lymphoma

This phase II study investigated the efficacy of alternating fludarabine/mitoxantrone/dexamethasone (FMD) with cyclophosphamide/doxorubicin/vincristine/prednisone (CHOP) chemotherapy for patients with high tumor burden, follicular non-Hodgkin's lymphoma. Maintenance interferon was given in a nonrandomized fashion, and a retrospective analysis of its impact was performed. A total of 87 patients were included (44 females and 43 males). The median age of patients was 56 years (range, 25–86 years). All patients had high tumor burden as defined by the Groupe d'Etude des Lymphomes Folliculaires (GELF) criteria. Eighty-four percent of patients (73/87) had stage III/IV disease and 99% of patients (86/87) had good performance status. The majority of patients had not been previously treated, with only 3 patients receiving prior oral alkylators or cyclophosphamide/vincristine/prednisone (COP). A total of 637 cycles of FMD/CHOP were administered and were well tolerated during this trial, the majority on an outpatient basis. The overall response rate was 95% (79 complete response/unconfirmed complete response/partial response) in the 83 evaluable patients. Event-free survival (EFS) was 28.7 months, with time to progression (TTP) at 29 months and time to treatment failure at 41 months. Overall survival was not reached. Patients had similar EFS and TTP as patients in the French GELF trial with a shorter duration of chemotherapy. Patients with a lower International Prognostic Index (IPI) score had better EFS when compared to those with a higher IPI score (median EFS not reached versus 22.6 months). Serum β2-microglobulin levels were not a significant predictive factor. An informal analysis of interferon maintenance therapy suggests that patients who tolerated the immune modifier did better than those who did not. Alternating FMD/CHOP is a feasible and effective therapeutic option for patients with high tumor burden, low-grade non-Hodgkin's lymphoma. While this regimen may not offer dramatic benefit over FMD alone, it is beneficial in those patients for whom a prompt treatment response is needed.

Interferon-α treatment in multiple myeloma: Meta-analysis of 30 randomised trials among 3948 patients

After two decades of interferon (IFN) treatment in myeloma patients and many randomised clinical trials, no definite proof of its benefits exists. This meta-analysis of all available relevant published data tests the differences between IFN and control arms in a large patient population and addresses the issue of cost-effectiveness. Meta-analysis was performed on 17 trials among 2333 patients who received IFN-chemotherapy induction treatment or chemotherapy alone and on 13 trials among 1615 patients on IFN maintenance therapy or without treatment. Response rates and parameters of published Kaplan Meier relapse-free and overall survival curves were analysed. Patients in IFN arms showed significantly better results in all investigated parameters: IFN-chemotherapy induction treatment yielded 6.6% higher response rates (2P < 0.002) as well as 4.8-month and 3.1-month prolongations of relapse-free (P < 0.01) and overall survival (P < 0.01), respectively. Interferon maintenance therapy lead to 4.4-month (P < 0.01) and 7.0-month (P < 0.01) prolongations of relapse-free and overall survival, respectively. Meta-analysis of all IFN trials combined resulted in 4.6-month and 3.7-month IFN-related gains in relapse-free and overall survival, respectively. As early as 6 and 12 months after the start of IFN treatment, percentages of cumulative relapse-free and overall survival were always significantly higher in IFN trial arms. IFN drug expenses for a one-year survival gain, as determined from AUCs of best-fitted Gompertz functions of IFN and control survival curves, were estimated to be US$42,482.28 for induction therapy and US$18,968.16 for maintenance treatment. Significantly superior outcomes were consistently found in IFN trial arms by meta-analysis of published data. These results are in accordance with a concomittantly conducted meta-analysis on individual patient data but were much easier to accrue. Taking all our results into account. i.e., the consistently significant, although limited, improvement of clinical outcomes and its acceptable cost-effectiveness, IFN treatment of patients with multiple myeloma seems worthwhile to be considered.

Treatment of chronic hepatitis C in nonresponders to interferon monotherapy.

Sixty percent of patients fail to respond to interferon monotherapy. African-Americans with hepatitis C appear to respond less well to interferon monotherapy. Retreatment with a higher dose of consensus interferon for 48 weeks has led to a sustained virologic response rate of 13%. As a group, interferon nonresponders who breakthrough while on interferon monotherapy seem to have a more favorable response rate to a repeat course of treatment. Retreatment with interferon and ribavirin for 6 months in nonresponders led to a sustained virologic response rate of 21%. Preliminary results from two trials in the United States demonstrate similar treatment efficacy. There is now evidence that maintenance interferon therapy may also be beneficial in interferon monotherapy nonresponders.

A randomized, controlled trial of maintenance interferon therapy for patients with chronic hepatitis C virus and persistent viremia

Background & Aims: At least half of patients with chronic hepatitis C virus (HCV) fail to respond to interferon or interferon/ribavirin therapy. Histological improvement is observed in some nonresponders. We conducted a randomized, controlled trial to determine if maintenance interferon therapy could prevent histological progression in this subset of nonresponders. Methods: Fifty-three patients with chronic HCV were enrolled. All were HCV-RNA positive after 6 months of treatment with interferon alfa-2b but had a histological response. Twenty-seven of the patients were randomly assigned to continue interferon (3 MU 3 times weekly) for 24 months; 26 patients discontinued treatment and were observed prospectively. Alanine aminotransferase (ALT) level and HCV-RNA titer were monitored, and liver biopsy was repeated every 12 months. Results: Before interferon therapy, the 2 groups were well matched for all demographic factors, serum ALT (94.0 ± 15.6), log HCV-RNA titer (5.85 ± 0.15 copies/mL), histology score (9.5 ± 0.2), and percentage with cirrhosis (25%). After 6 months of treatment, significant reductions ( P < 0.05) in serum ALT level (62.6 ± 9.6), log HCV-RNA titer (4.79 ± 0.13 copies/mL), and hepatic inflammation (4.0 ± 0.2) were observed. These improvements were maintained in the patients randomized to continue interferon. Stopping treatment was associated with an increase in serum ALT, log HCV-RNA, and hepatic inflammation back to baseline. After 30 months of treatment, mean fibrosis score declined from 2.5 to 1.7 and 80% of patients had histological improvement ( P < 0.03). Discontinuation of interferon was associated with an increase in mean fibrosis score from 2.2 to 2.4 and worsening of hepatic histology in 30% of patients ( P < 0.01). Conclusions: These data support the hypothesis that maintenance interferon may prevent histological progression of chronic HCV in patients who remain viremic. GASTROENTEROLOGY 1999;117:1164-1172

Chronic Myelogenous Leukemia in Chronic Phase for 16 Years: Ongoing Hematological Remission and Late Minor Cytogenetic Response under Minimal Interferon Maintenance Therapy

Philadelphia chromosome-positive chronic myelogenous leukemia was diagnosed in a now 37-year old woman 16 years ago. Induction therapy with hydroxyurea and busulphan led to hematological remission lasting for about 4 months without treatment. Then, intermittent busulphan over a 7 years' period, and subsequently, alpha-interferon was given, of which ever decreasing doses (currently 3.5 megaunits interferon-alpha-2c once every 14 days) have been required to keep leukocyte counts in the target range. Although no major cytogenetic response was achieved by maintenance therapy, the patient has now been in an ongoing chronic phase of disease for 16 years. This is a rare case of indolent chronic myelogenous leukemia, in which, for undefined reasons, the leukemic cells have not aquired the capacity to transform leading to disease acceleration, which usually is imminent after a few years.

Weekly systemic combination of cisplatin and interferon α2a in diffuse malignant pleural mesothelioma

The treatment of diffuse malignant pleural mesothelioma (DMPM) remains grim. Neither surgery, radiotherapy nor chemotherapy can be considered as a standard therapy. Immunotherapy with interferon (IFN) in combination with chemotherapy may be an interesting new approach. In 13 consecutive patients with DMPM, we used a weekly combination of cisplatin (CDDP) (60 mg/m 2; day 2) and IFN α2a (6 MU/day; days 1–4) in a protocol of two cycles of 4 weeks on/4 weeks off followed by 3 weeks on/3 weeks off. Total treatment duration was thus 25 weeks. In responders, IFN as maintenance monotherapy was continued for a further 6 months. There were nine males and four females with an average age of 65.3 years (range 51–72 years). Eleven had epithelial, one had mixed and one had a sarcomatoid form of DMPM. Five patients were classified as stage II, six as stage III and two as stage IV, as per the International Mesothelioma Interest Group. Thirty-five cycles were administered with a median of three cycles/patient (range 0.75–4). The median total cumulative dose of CDDP was 596 mg/m 2 (range 114–861) and that of IFN α2a was 264 MU (range 72–336). Four patients received IFN maintenance therapy, one for 3 months and three for 6 months. One patient had a complete response, four had a partial response, six had a stable disease and the disease progressed in one. One patient was non evaluable for response. All patients were assessable for toxicity. Hematological toxicity was the most frequently observed but was manageable (grade 3 anemia in five patients, grade 3 thrombocytopenia in three patients, grade 3 neutropenia in five patients). Grade 1 renal toxicity was observed in six patients, grade 2–3 asthenia in six patients and an average 5-kg weight loss was noted in nine patients. In conclusion, systemic combination of CDDP and IFN α2a in large doses is effective at the expense of non-negligible toxicity.

Sensitivity analyses of Q-twist model for interferon maintenance therapy in multiple myeloma

Sensitivity analyses of Q-twist model for interferon maintenance therapy in multiple myeloma

Randomized trial of interferon maintenance in multiple myeloma: a study of the National Cancer Institute of Canada Clinical Trials Group.

To determine whether interferon maintenance therapy improves overall survival and response duration in patients with multiple myeloma who have responded to induction therapy with melphalan and prednisone. In a multicenter trial, patients with symptomatic clinical stage I and stage II and III multiple myeloma were registered at diagnosis and those who responded to melphalan-prednisone (MP) were randomized either to receive interferon (2 mU/m2) subcutaneously three times per week or no maintenance. MP was discontinued in both groups once a stable response plateau of the monoclonal protein was reached. Interferon was continued until relapse, and then was restarted on subsequent response to MP. Interferon toxicity was recorded using a self-report diary. Survival and response duration were calculated using life-table methods, and were adjusted in the analysis for imbalances in baseline prognostic factors. Four hundred two patients were registered and 176 responders were randomized (85 to interferon and 91 to control). At a median follow-up time of 43 months, the median survival duration was 43 months for interferon and 35 months for control (P = .16), but when adjusted for chance imbalances in baseline prognostic factors (mainly performance status), the median survival duration was 44 months and 33 months for interferon and control, respectively (P = .049). Progression-free survival from randomization to first relapse also favored interferon (unadjusted P < .002; adjusted P < .003). Interferon toxicity caused 58% of patients to reduce their dose, of which 84% were able to return to the initial dose; 14% had to discontinue interferon treatment. Interferon maintenance therapy improves progression-free and overall survival of patients with multiple myeloma who respond to melphalan and prednisone. Toxicity is substantial and must be weighed by patients against the potential benefits in response duration and survival.

Interferon maintenance therapy for patients with chronic lymphocytic leukemia in remission after fludarabine therapy

Many patients with chronic lymphocytic leukemia (CLL) achieve remission after treatment with fludarabine chemotherapy. Most of these patients, however, later experience relapse. In addition, immunologic deficits may persist even in patients in complete remission; lymphopenia, predominantly involving the CD4 population, is universal after fludarabine therapy. We used recombinant alpha interferon (IFN-alpha) maintenance therapy in patients with CLL who achieved remission in response to fludarabine therapy to determine its effect on residual disease, assessed by either bone marrow biopsy or flow cytometry, and on immune restoration. Thirty-one patients were treated with IFN-alpha (3 x 10(6) U by subcutaneous injection three times weekly). Twenty-two patients (71%) were in complete remission (CR) and nine (29%) were in partial remission (PR). Of the 22 patients in CR, 21 (95%) had evidence of residual disease at the start of IFN-alpha therapy. Low CD4 levels were noted in 93% of patients, low IgG levels in 45%, and anergy or hypoergy in 52%. Only one patient in PR achieved a CR on IFN-alpha therapy: the only patient who had had no prior fludarabine but had been treated with chlorambucil and prednisone. All patients in CR with minimal residual disease had persistent disease after IFN-alpha treatment. There were no increases in CD4 counts or IgG levels; three patients with borderline responses to skin testing had an increase in the number of positive tests while on IFN-alpha. The time to progression was no different in patients treated with IFN-alpha than in a historical control group of patients who had received no further therapy after fludarabine. In summary, the use of IFN-alpha maintenance did not eradicate residual disease, restore immune function, or prolong remissions in patients with CLL responsive to fludarabine.

Interferon-alpha for induction and maintenance in multiple myeloma: Results of two multicenter randomized trials and summary of other studies

Interferon (IFN) treatment trials in multiple myeloma have yielded discordant results regarding response rates, maintenance duration, and survival times. Further randomized trials and global evaluations of available data are urgently needed for clarification. 256 patients participated in a randomized trial, 125 on IFN + VMCP, and 131 on VMCP alone. 100 patients were randomized to IFN maintenance (n = 46) or were untreated controls (n = 54). Global evaluations are based on 1,518 patients in induction and 924 in maintenance trials. The induction trial demonstrated a significantly (p < 0.05) lower rate of progressive disease under IFN + VMCP (10.6%) than under VMCP (22.9%), but this benefit was limited to stage I or II patients. Median progression-free survival was longer in the IFN + VMCP arm (23.2 months vs. 15.8 months); median overall survival did not differ significantly (38.9 vs. 30.2 months). The IFN maintenance treatment trial showed significantly superior results in the IFN arm versus controls (median maintenance duration: 17.8 months and 8.2 months (p < 0.01), survival: 50.6 and 34.4 months (p < 0.05), respectively). Previous IFN treatment increased the benefits of IFN maintenance therapy. Adverse effects of IFN during induction were hematologic toxicity, fever, and infections, requiring dose reductions. Toxic effects of IFN maintenance treatment were mild. Global evaluations of randomized trials showed small but significant benefits of combined IFN induction therapy and significantly prolonged maintenance duration and survival under IFN maintenance. Presently available data support the use of IFN maintenance treatment because it significantly prolongs maintenance duration and survival. IFN added to induction chemotherapy resulted in minor improvements at the expense of increased toxicity, highlighting the need for better induction regimens.

Interferon alfa‐2b versus no maintenance therapy during the plateau phase in multiple myeloma: a randomized study

This clinical trial was designed to investigate if maintenance therapy with alfa-interferon could prolong the plateau phase in patients with multiple myeloma. In addition, the tolerability of interferon treatment and its effect on survival were evaluated. From September 1987 to September 1989 a total of 314 patients were accrued to a multi-institutional randomized clinical trial. All patients entered into the protocol received standard melphalan-prednisone (MP) induction therapy. Response was noted in 184 (59%) and a plateau phase achieved in 155 (49%). From the latter group, 125 eligible patients were randomized to either interferon alfa-2b or no maintenance. The patients were followed for an average of 51 months (minimum 36 months) from the time of randomization. The plateau phase was significantly prolonged in the group of patients treated with interferon (median 13.9 v 5.7 months from the time of randomization; P < 0.0001). The interferon therapy was tolerated fairly well, moderate granulocytopenia and a chronic fatigue syndrome being the most frequent side-effects (22% v 18% W.H.O. grade 3 toxicity). The median survival from randomization was almost identical in both groups (36 v 35 months). The study shows that interferon maintenance therapy given to multiple myeloma patients who have achieved a response to initial treatment with MP prolongs the plateau phase duration with tolerable toxicity. The clinical value of this finding should be interpreted with caution, because survival was not prolonged. Further studies are required to clarify the role of interferon in the treatment of multiple myeloma.

Myeloma during a decade: Clinical experience in a single centre

One hundred and fifty-six patients with multiple myeloma were treated over a period of 12 years at St. Bartholomew's Hospital. The progress of the disease was affected in 96/156 patients (61%). Response was defined as achieving a plateau of M component. A partial or complete response was seen in 68/120 patients treated conventionally (56.5%), and in 28/36 patients treated with high-dose therapy (77.7%). The median survival of the group as a whole was 20 months, with a 2-year survival of just over 40%. In the 36 patients treated with high-dose therapy, median survival was 6 years, and in a small group who have had maintenance Interferon therapy, the median has not yet been reached. In a univariate analysis, age, intensity of therapy, haemoglobin and creatinine levels were significant, but multivariate analysis showed that only age and intensity of therapy were independent predictors for survival. The outlook for relapsed patients who showed progression of disease remains poor, but palliation was best achieved by steroid and Interferon in combination. Patients who achieve complete responses and are maintained on Interferon appear to be doing better both in terms of freedom from symptoms and in survival, and methods to enable an elderly population to tolerate this form of therapy need to be explored.

Interferon maintenance therapy for small cell lung cancer: Long term survival : K. Mattson ∗, A.Niiranen ∗, S. Pyrhönen ∗∗, P. Maasilta ∗, M. Kajanti ∗∗, K. Cantell#, ∗Dept of Pulmonary Medicine, ∗∗Dept of Radiotherapy and Oncology, Helsinki University Central Hospital and #National Public Health Institute, Helsinki, Finland

Interferon maintenance therapy for small cell lung cancer: Long term survival : K. Mattson ∗, A.Niiranen ∗, S. Pyrhönen ∗∗, P. Maasilta ∗, M. Kajanti ∗∗, K. Cantell#, ∗Dept of Pulmonary Medicine, ∗∗Dept of Radiotherapy and Oncology, Helsinki University Central Hospital and #National Public Health Institute, Helsinki, Finland

Interferon alfa-2b with VMCP compared to VMCP alone for induction and interferon alfa-2b compared to controls for remission maintenance in multiple myeloma: Interim results

The present trial was designed to evaluate whether interferon (IFN) combined with standard induction chemotherapy and/or interferon remission maintenance treatment improve treatment results in patients with multiple myeloma. Up to now 89 patients have received IFN plus vincristine/melphalan/cyclophosphamide/prednisolone (VMCP) as induction therapy, and 86 conventional VMCP. The proportion of patients with progressive disease was significantly lower ( P < 0.005) under IFN + VMCP as compared to the VMCP treatment group. Survival times were significantly longer ( P < 0.02) after IFN + VMCP induction therapy than after VMCP alone. In the second phase of this investigation, 33 progression-free myeloma patients were assigned to receive IFN as maintenance therapy, and 41 patients served as untreated controls. Patients maintained with IFN showed a tendency towards increased progression-free survival. Haematological side effects were observed significantly more often in patients receiving IFN, with more severe haematological toxicity in patients on the combined IFN + VMCP regimen and an increased number of patients with mild haematological toxicity in the group maintained with IFN. Other side effects, such as fever and fatigue, remained within tolerable limits. In conclusion, the preliminary results of this current clinical trial indicate significant advantages of combined IFN + VMCP induction treatment in terms of reduced disease progression and prolonged survival and possible benefits of IFN maintenance therapy in patients with multiple myeloma.

Randomized study of chlorambucil (CB) compared to interferon (alfa-2b) combined with CB in low-grade non-Hodgkin's lymphoma: An interim report of a randomized study

Alpha interferon has shown initial promise in the treatment of low-grade non-Hodgkin's lymphoma (NHL), especially with the nodular form of the disease. The present study enrolled 70 NHL patients who received either chlorambucil (CB; 10 mg/day) or CB plus interferon alfa-2b (5 million units (MU)/m 2 subcutaneously three times a week). Among 63 evaluable patients, similar response rates (62.1% and 64.7% respectively) were recorded for the treatment arms. In patients receiving no maintenance therapy, those who received interferon alfa-2b during the induction phase showed a favourable trend in terms of incidence of relapse compared to those who had received chlorambucil alone. During maintenance therapy with interferon alfa-2b, no significant differences in the occurrence of relapse have yet been seen compared to patients on no maintenance therapy. A longer observation period is needed to make a definitive conclusion about the usefulness of interferon maintenance therapy and to evaluate further the effects of the combined schedule of chlorambucil and interferon induction on the duration of remission.

Alpha interferon maintenance therapy in patients with low-grade non-Hodgkin's lymphomas after cytoreductive chemotherapy with prednimustine and mitoxantrone

A combination of prednimustine 100 mg/m 2/day orally, days 1–5, and mitoxantrone 8 mg/m 2/day intravenously, days 1 and 2, was administered to 19 patients with advanced low-grade non-Hodgkin's lymphoma after failure on or relapse after standard chemotherapy. The prednimustine and mitoxantrone (PmM) regimen was repeated every 4–6 weeks to a maximum of six cycles. Thirteen patients, achieving a complete (4) or partial (9) remission (CR or PR), received two additional courses for consolidation followed by interferon alfa-2b 5 million units (MU) subcutaneously (s.c.) three times weekly until progression or relapse. At the present time, remission duration ranges from 4.5+ to 17.5+ months, with a median of 14.5 months. In a historical comparison to unmaintained first remission preceding the PmM/interferon trial, a tendency towards a longer period of freedom from progression was apparent in the 13 patients receiving interferon maintenance treatment during their second PR or CR. These data provided the basis for a currently ongoing multicentre study randomly comparing initial chemotherapy with PmM versus cyclophosphamide/vincristine (Oncovin)/prednisone (COP) in patients with advanced centroblastic-centrocytic and centrocytic non-Hodgkin's lymphomas, followed by a second randomization in CR and PR patients for maintenance with alpha interferon versus observation only.