Monica Marconi

Common and rare side-effects of low-dose thalidomide in multiple myeloma: focus on the dose-minimizing peripheral neuropathy

Objectives:  Thalidomide has demonstrated a remarkable efficacy in the treatment of multiple myeloma but its use may cause several toxicities. We have investigated the common and rare side‐effects, especially analysing peripheral neuropathy, in order to optimise the thalidomide dose for minimizing this harmful side‐effect.

Thalidomide-dexamethasone versus Interferon-alpha-dexamethasone as maintenance treatment after ThaDD induction for multiple myeloma: a prospective, multicentre, randomised study

Maintenance therapy was explored in multiple myeloma (MM) patients after conventional thalidomide, dexamethasone and pegylated liposomal doxorubicin (ThaDD). Patients with newly or relapsed MM obtaining at least minor response after 6 ThaDD courses, were randomised to receive α‐interferon (IFN) 3 MU 3 times a week or thalidomide 100 mg daily until relapse. Both groups also received pulsed dexamethasone 20 mg 4 d a month. Fifty‐one patients were randomized in the IFN‐dexamethasone (ID) arm and 52 in the thalidomide‐dexamethasone (TD) arm. The characteristics of two groups were similar. A significantly better 2‐years progression‐free survival (PFS; 63% vs. 32%; P = 0·024) and overall survival (84% vs. 68%; P = 0·030) was observed in the thalidomide arm. In high‐risk patients and in those achieving less than very good partial response after induction, TD fared better in term of PFS. Main side effects were peripheral neuropathy and constipation in TD group, fatigue, anorexia and haematological toxicity in ID arm. There was a 21% probability of discontinuation at 3 years in the thalidomide arm and 44% in the IFN arm (P = 0·014). Low‐dose thalidomide plus pulsed low‐dose dexamethasone after conventional thalidomide combination‐based therapy was also feasible in the long term, enabling significantly better residual disease control if compared with a standard maintenance therapy.

Thalidomide–dexamethasone plus pegylated liposomal doxorubicin vs. thalidomide–dexamethasone: a case-matched study in advanced multiple myeloma

Objectives:  Nearly all patients with multiple myeloma (MM) relapse or become refractory to front‐line therapy. Several salvage therapies have been explored, but the optimal combination regimen has not been defined. We performed a case‐matched study comparing patients with relapsed/refractory MM receiving thalidomide–dexamethasone alone or the combination thalidomide–dexamethasone–liposomal pegylated doxorubicin.

Technetium-99m sestamibi scintigraphy is sensitive and specific for the staging and the follow-up of patients with multiple myeloma : a multicentre study on 397 scans

We evaluated the additional benefit of Technetium99‐sestamibi (99mTc‐MIBI) scanning in comparison with standard X‐ray techniques for multiple myeloma patients either at diagnosis or during follow‐up. Between February 2001 and January 2005, 397 whole body scans were acquired. On 229 scans performed at diagnosis, 146 (64%) were positive and 81 cases have discordant X‐ray results. The sensitivity of 99mTc‐MIBI and X‐ray were 77% and 45% respectively. As a result of 99mTc‐MIBI, 40% of asymptomatic myeloma patients were up‐staged. The positivity of 99mTc‐MIBI correlated significantly with all of the most relevant clinical and biological parameters. Multivariate analysis selected only high reactive C protein (P = 0·0005), bone marrow infiltration (P = 0·02) and bone pain (P = 0·002) as factors affecting 99mTc‐MIBI pattern. In 22 patients with solitary myeloma, 99mTc‐MIBI was positive in 86% of cases and detected more disease sites than X‐ray. Among 168 scans performed during follow‐up, 99mTc‐MIBI presented high specificity in patients showing a complete response (CR; 86%), and correlated with myeloma activity and with response to therapy. At multivariate analysis, a positive pattern correlated with bone marrow infiltration (P = 0·002) and disease status other than CR (P = 0·03). We conclude that 99mTc‐MIBI scanning is an additional diagnostic tool with a high specificity for the staging and the follow‐up of multiple myeloma patients.

Risk assessment of patients with hematologic malignancies who develop fever accompanied by pulmonary infiltrates: a historical cohort study.

The mortality rate associated with fever accompanied by pulmonary infiltrates after chemotherapy for hematologic malignancies remains higher than the corresponding rate associated with febrile neutropenia without pulmonary infiltrates. Nonetheless, few studies have focused on the factors that predict outcome for patients with lung infiltrates. The purpose of the current study was to construct a risk model for clinical use by assessing the factors that affect outcome for patients with fever and pulmonary infiltrates.

Serum C-Reactive Protein at Diagnosis and Response to Therapy Is the Most Powerful Factor Predicting Outcome of Multiple Myeloma Treated with Thalidomide/Anthracycline—Based Therapy

BACKGROUND Few studies have focused on factors affecting outcome in patients with multiple myeloma (MM) treated with thalidomide-based therapy. We investigated factors affecting response, progression-free survival (PFS), and overall survival (OS) in patients with MM treated with the thalidomide, dexamethasone, and pegylated liposomal doxorubicin (ThaDD) regimen with the aim to select patients benefiting more from this therapy. PATIENTS AND METHODS Sixty-six patients with MM were treated first line with the ThaDD regimen. We analyzed demographics and disease-related characteristics to search for factors affecting response (> or = very good partial remission [VGPR] vs. < VGPR], PFS, and OS. RESULTS Overall, 45 patients (68%) showed response > or = VGPR; median TTP and OS were 23.5 months and 35.5 months, respectively. Multivariate analysis selected only serum C-reactive protein (sCRP) as a predictive factor for response (P < .0001). By multivariate analysis, normal sCRP level (P = .001) and response to treatment > or = VGPR (P = .007) were found to be associated with longer PFS. The factors that remained significantly associated with a longer OS when assessed by multivariate analysis were normal sCRP level (P = .005) and response to therapy > or = VGPR (P = .019). CONCLUSION Serum C-reactive protein before therapy and response after therapy are the only factors useful in identifying patients benefiting from anthracycline/thalidomide-based therapy.

Comparison of two regimens for the treatment of elderly patients with acute lymphoblastic leukaemia (ALL).

Acute lymphoblastic leukemia (ALL) represents a rare malignancy in the elderly and few authors have specifically focused on the treatment of ALL in this setting. We recently published the results of a prospective phase II study comprising an induction therapy with vincristine, Daunoxome and dexamethasone (VDXD) given to 15 patients aged ⩾̸ 60 years. Here, we update the results after enrolling 17 patients, and we compare these with the results obtained in 17 elderly patients treated according to the GIMEMA ALL 0288 protocol. With the VDXD combination, elderly ALL had a higher CR rate (76.5%) than with the 0288 protocol (41%), and it was likely due to both lower induction mortality (17.5% vs. 35%) and a less resistant disease (6% vs. 24%). Infectious complications were more frequent with the VDXD combination whereas non-hematological side effects were comparable. Despite the similar DFS obtained with the two induction treatments, median EFS (3.9 months with 0288 vs. 12.8 with VDXD; p = 0.0486) and OS (4.5 vs. 21 months; p = 0.0239) were significantly higher with the VDXD regimen. In elderly ALL patients the administration of high-dose daunorubicin as a liposomal compound is feasible and seems able to improve CR rate, EFS and OS without increase in toxicity.

Infectious Complications in Adult Acute Lymphoblastic Leukemia (ALL): Experience at One Single Center

Literature provides no specific data concerning the type and the risk factors for infection in adult patients with acute lymphoblastic leukemia (ALL). We retrospectively analyzed 97 adult ALL patients who underwent conventional chemotherapy during a 14-year period with the aim to assess the incidence and the factors affecting onset and outcome of infections. We found that during induction therapy 50% of patients developed infection, mainly caused by gram-negative bacteria and with a mortality rate of 11%. In multivariate analysis age > 60 years was significantly associated with more infections (P = 0.04) and higher related mortality (P = 0.03). Moreover, in 22% of patients infectious complications occurred during consolidation or maintenance therapy. Mortality rate of these infections, mostly due to opportunistic pathogens, was 16%. Factors affecting mortality was the cumulative dose of methylprednisolone given during induction therapy ( < or = 2600 mg = 31% vs. > 2600 mg = 69%; P = 0.03). Among neutropenic patients, adults with ALL represent a peculiar population since they frequently develop gram negative infections during induction and opportunistic infections during post-remission treatments. Advanced age and high-dose methylprednisolone result the major risk factors for infection related mortality in the former therapeutic phase and in the latter one, respectively.

Gemcitabine Alone or Combined with Cisplatin in Relapsed or Refractory Multiple Myeloma

Gemcitabine is a pyrimidine nucleoside analog with antitumor activity against solid tumor malignancies and leukemia. We evaluated its activity as a single agent and combining it with cisplatin in relapsed-refractory multiple myeloma (MM). Sixteen patients with advanced MM received intravenous gemcitabine 1250 mg/mq (days 1, 8 and 15) as a single agent for a total of 3 monthly courses. The responders received another three courses, and the non-responders received three courses of gemcitabine 1000 mg/mq (days 1, 8 and 15) plus cisplatin 80 mg/mq (day 1). No grade 4 hematological toxicity was seen after gemcitabine treatment, whereas ≥ 3 grade neutropenia and thrombocytopenia were seen in 21 and 13% of the gemcitabine-cisplatin infusions, respectively. Non-hematological toxicity was negligible for both the regimens. After three courses of gemcitabine as a single agent, the response rate was 31% (1 complete response, 1 partial response and 3 minimal response). Eight patients (50%) achieved stable disease and 3 (19%) had disease progression. Ten patients received gemcitabine-cisplatin and were evaluable for the response. Two patients progressed, four maintained stable disease whereas four patients, unresponsive to gemcitabine, obtained a response (3 partial response and 1 minimal response). With a median follow-up of 13 months (range 8-17.5), 7 patients (44%) died, 5 (31%) had disease progression, 1 (6%) relapsed, 1 was still in partial response (+11 months) and 2 (13%) had a stable disease. Median time to treatment failure (TTF) was 8 months (CI 95%: 7.6-8.4) and median overall survival (OS) was 16 months (CI95%: 10-22). These results showed that gemcitabine and gemcitabine-cisplatin were feasible regimens and well tolerated in advanced relapsed-refractory MM. The response rates, the TTF and OS were similar to other salvage chemotherapy regimens; nevertheless, the quality of response was modest particularly after gemcitabine alone. Better results might be obtained combining gemcitabine with other chemotherapy compounds or with biologically based therapies.