Myeloma and Lymphoma: Relapsed and Refractory Diffuse, Large B-Cell Lymphoma

Posted by James

Speaker: Thomas C. Shea, University of North Carolina School of Medicine, Chapel Hill, North Carolina

Salvage therapy for relapse of diffuse, large B-cell lymphoma depends on the answers to several questions:

• Which relapse is it?
• Which therapies have been used in the past?
• What was the last interval of response?
• Was the prior response complete or partial?
• What are the patient’s characteristics and profile (age, organ function, medical history, and comorbidities?)

A study was conducted to determine the response rate and toxicity of GDP (gemcitabine, dexamethasone, cisplatin [Plati-nol®]) chemotherapy for recurrent or refractory NHL. The primary endpoint was a complete or partial response after two cycles and followed by HSCT. buy antibiotics in canada

GDP was an active regimen in patients with large B-cell lymphoma along with acceptable toxicity to outpatients. In patients with recurrent or relapsed NHL, the response rates (progression-free and overall survival) with R-ICE (rituximab, ifosfamide, carboplatin, etoposide) chemotherapy was greater than with ICE chemotherapy alone.

Initial therapy dictates the outcome in elderly patients with diffuse, large B-cell lymphoma. The outcome of 94 consecutive elderly patients treated for aggressive lymphoma without a low-grade component showed that the median survival was 26 months and the five-year overall survival was 39% (range, 27%-50%). Twenty patients had disease that was refractory to first-line CHOP or CHOP-like therapy, and only one of 20 patients was alive with active lymphoma. This study suggests that conventional-dose, second-line chemotherapy yielded disappointing results for these elderly patients.

A randomized trial of high-dose therapy plus autologous stem-cell support with the standard regimen of CHOP was conducted. The patients, aged 15 to 60 years, had untreated aggressive lymphoma with a low, a low-intermediate, or high-intermediate risk of death (i.e., with a maximum of two adverse prognostic factors), according to the age-adjusted International Prognostic Index. cialis canadian pharmacy

The primary outcome was event-free survival at five years. High-dose chemotherapy with autologous stem-cell support was superior to CHOP in adults with disseminated aggressive lymphoma. However, rituximab was not used in this study.

The results of high-dose chemotherapy and autologous HSCT (autotransplantation) in patients with diffuse aggressive NHL who had not achieved a complete response with conventional chemotherapy were of interest. Seventy-nine (44%) of 184 patients achieved complete response or a complete response with residual imaging abnormalities of unknown significance after autotransplantation.

Thirty-four (19%) of 184 patients achieved partial responses, and 55 (31%) of these patients had no response or progressive disease.

The researchers concluded that high-dose chemotherapy and autologous HSCT should be considered for patients with diffuse, aggressive NHL who do not achieve a complete response but who are still chemotherapy-sensitive and who would otherwise be appropriate candidates for transplantation.

In summary, salvage therapy for diffuse, large B-cell lym-phoma suggests that patients may benefit from the addition of antibody therapy for less than three months before HSCT. canadian antibiotics

Therapies for Mantle-Cell Lymphoma

Speaker: Michael E. Williams, University of Virginia School of Medicine, Charlottesville, Virginia

The key concerns in treating mantle-cell lymphoma are the need to understand (1) the biological and prognostic subtypes, (2) the best initial therapy, (3) the best treatment options for relapsed disease, (4) the role and timing of HSCT, and (5) emerging therapies.

No one initial therapy has proved superior, although several combinations have been partially successful. The combination of rituximab plus CHOP (R-CHOP) has been fairly successful, with a 96% overall response rate and a 48% rate of complete remission. CHOP, CVP, fludarabine, chlorphosphamide, F-IDA (fludarabine, idarubicine), and PEP-C (prednisone, etoposide, procarbazine, cyclophosphamide) have also been used. Response durations usually last for eight months to a year.

A randomized trial was conducted to compare the combination of R-CHOP with CHOP alone as first-line therapy for advanced-stage mantle-cell lymphoma. One hundred twenty-two previously untreated patients were assigned to six cycles of CHOP (n = 60) or R-CHOP (n = 62). Patients up to 65 years of age who achieved a partial or complete remission underwent a second randomization to either myeloablative radio-chemotherapy, followed by autologous HSCT, or interferon-alpha (IFN-a) maintenance therapy. All patients older than 65 years of age received IFN-a maintenance therapy. R-CHOP was significantly superior to CHOP in terms of overall response rate (94% vs. 75%) (P = .0054), complete remission rate (34% vs. 7%; P = .00024), and time to treatment failure (median, 21 vs. 14 months) (P = .0131). No differences were observed in progression-free survival. eriacta 100 mg

In conclusion, combined immunochemotherapy with R-CHOP brought about a significantly higher response rate and a prolonged time to treatment failure, compared with chemotherapy alone. Hence, R-CHOP may serve as a new baseline regimen for advanced mantle-cell lymphoma, but further improvement is needed in terms of novel strategies that can be used during remission.

Rituximab plus Hyper-CVAD. A prospective phase 2 trial was conducted to determine the response, failure-free survival, and overall survival rates and toxicity of rituximab plus an intense chemotherapy regimen in patients with previously untreated aggressive mantle-cell lymphoma. Patients received rituximab plus fractionated hyper-CVAD (cyclophosphamide, vincristine, doxorubicin [Adriamycin®], dexamethasone) (considered one cycle), alternating every 21 days with ritux-imab plus high-dose methotrexate-cytarabine (considered one cycle) for a total of six to eight cycles.

Of 97 assessable patients, 97% responded; 87% achieved a complete remission or unconfirmed complete remissions. With a median follow-up time of 40 months, the three-year failure-free rate was 64%, and the overall survival rate was 82%, without a plateau in the curves.

It was concluded that rituximab plus hyper-CVAD, alternating with rituximab plus high-dose methotrexate and cytar-abine, was effective in untreated, aggressive mantle-cell lym-phoma. Toxicity was significant but expected.
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Rituximab plus FCM. In a prospective, randomized study in patients with relapsed mantle-cell lymphoma, rituximab improved the prognosis when it was combined with chemotherapy. A total of 147 patients received four courses of chemotherapy with fludarabine 25 mg/m2 on days one to three, cyclophosphamide 200 mg/m2 on days one to three, and mitoxantrone 8 mg/m2 on day one (FCM), alone or combined with rituximab 375 mg/m2 (R-FCM). The R-FCM arm experienced better progression-free survival (P = .0381) and overall survival (P = .003).

In patients with follicular lymphoma, progression-free survival was significantly longer in the R-FCM arm (P = .0139). In patients with mantle-cell lymphoma, a significantly longer overall survival time was observed with R-FCM (P = .0042). There were no differences in clinically relevant ADEs in either study arm. Hence, the addition of rituximab to FCM chemotherapy significantly improved the outcome of relapsed or refractory mantle-cell lymphoma.

Bortezomib. In four studies of relapsed mantle-cell lym-phoma, bortezomib showed 40% to 50% efficacy in response rates over a period of months to two years. In one study, when rituximab was given for four weeks, followed by thalidomide, all patients required dose reductions, from 400 mg, during maintenance. The overall response rate for 18 patients was 83%. kamagra uk

Temsirolimus. As an inhibitor of the mammalian target of rapamycin (mTOR), temsirolimus is under study for relapsed, refractory mantle-cell lymphoma. Table 1 presents additional novel therapies being studied for mantle-cell lymphoma.

Hodgkin’s Lymphoma

Speaker: Joseph M. Connors, British Columbia Cancer Agency, Vancouver, British Columbia

ABVD Chemotherapy. The gold standard of treatment for Hodgkin’s lymphoma includes four cycles of ABVD (doxo-rubicin, [Adriamycin®] bleomycin, vinblastine, dacarbazine) for stage IA, IIA low-bulk tumors and six to eight cycles for bulky tumors. For the 80% of patients with advanced disease but without a large number of adverse prognostic factors, standard multiagent chemotherapy with the well-established ABVD regimen provides the best balance of effectiveness and minimization of toxicity. More intensified regimens currently under investigation are appropriate for the 20% of patients with numerous adverse prognostic factors.

BEACOPP Chemotherapy. A BEACOPP regimen (bleo-mycin, etoposide, doxorubicin [Adriamycin®], cyclophos-phamide, vincristine [Oncovin®], procarbazine, prednisone) was developed to investigate the potential of moderate-dose escalation of conventional polychemotherapy to improve the unsatisfactory treatment results in advanced-stage disease. Following pilot studies, the randomized trial demonstrated that BEACOPP, at the baseline dose, attained superior failure-free survival to COPP/ABVD and that a dose escalation brought about a further marked improvement. Toxicity was severe but manageable. The BEACOPP regimen is highly effective, and moderate-dose escalation results in a further worthwhile improvement in tumor control. kamagra soft tablets

Summary. The prognosis for elderly patients with advanced disease, in contrast to that of younger patients, has not improved substantially over the last 20 years. The most effective method of therapy for refractory or relapsed Hodgkin’s lym-phoma is still unresolved in terms of whether to use high-dose or conventional aggressive chemotherapy. High-dose chemotherapy, followed by autologous HSCT (BEAM [etopo-side, cytarabine, melphalan]-HSCT), is frequently used to treat patients with relapsed disease and may be the best strategy. Today, it is not enough to focus solely on a cure for this disease; the treatment program must maximize the chance of cure and minimize late-stage toxicity.