Haematological Malignancies
Table 3: First-line Treatment – Autologous Haematopoietic Stem Cell Transplantation versus Conventional Chemotherapy
Author Lenz 200426
Number of Patients Therapy 114
126 Lenz 2004*27
195 236
Sebban 2006**28
192 209
Ladetto 200829
68 66
Gyan 200930
86 80
Auto HSCT CHOP/MCP
Auto HSCT CHOP/R-CHOP
Auto HSCT CHVP-I
Auto HSCT R-CHOP
Auto HSCT CHVP-I
92 51 108
17 14
85 62
81*** 69***
Follow-up (Months) CR (%) 51
52.1 21.4
44 NS
PFS (%) 64.7
33.3
p
p
p=0.11 61 28
p
p=0.004 NS
76 71
p=0.53 81 80
p=0.96 76 80
p=0.55
3.8 0
p=0.0248 1 2
p=NS 6.6 1.7
p=0.111 7 1
p=0.01
AML = acute myeloid leukaemia; Auto HSCT = autologous haematopoietic stem cell transplantation; CHOP = cyclophosphamide, doxorubicin, vincristine, prednisone; CHVP-I = cyclophosphamide, adriamycin, etoposide, prednisolone, interferon; CR = complete response; MCP = mitoxantrone, chlorambucil, prednisone; MDS = myelodysplastic syndrome; NS = not stated; OS = overall survival; PFS = progression-free survival; R-CHOP = rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone. *Follicular lymphoma (FL) 75%; **FL 84%; ***Overall response rate.
was not optimal from a current point of view. Therefore, the prognostic relevance of autologous HSCT compared with current chemoimmunotherapy is being evaluated in a phase III trial by the German Low-grade Lymphoma Study Group (GLSG): after induction treatment with six cycles of CHOP/R-CHOP, responding patients
Interestingly, a small prospective phase II trial (n=31 patients with FL or mantle cell lymphoma) provided evidence for a potential effect of post-autologous HSCT rituximab maintenance. One single course of rituximab helped to prevent relapses by the elimination of minimal residual disease approved by PCR analysis and may translate into improved event-free survival (EFS).31
In a randomised phase III study R-bendamustin (R-B) appeared to be superior to R-CHOP with regard to CR rate (40 versus 30%) and EFS (54.8 versus 34.8 months). In addition, the bendamustin arm provided a significantly better toxicity/tolerability profile.32
To date, chemoimmunotherapy alone has not yet been compared in randomised trials with the promising option of consolidation radioimmunotherapy. In order to evaluate the best first-line treatment in patients with FL, the US Intergroup trial compared R-CHOP with CHOP followed by 131I-tositumomab in a randomised phase III trial that closed in 2009. In summary, in symptomatic patients, chemoimmunotherapy is the current treatment of choice based on five randomised trials with no consensus on the best chemotherapy arm.11–15
Therefore, different approaches for second-line treatment have been evaluated: chemoimmunotherapy, radioimmunotherapy, autologous and allogeneic HSCT.
60
Salvage Treatment Strategies in Relapsed/Refractory Follicular Lymphoma In patients with relapsed or recurrent FL, conventional chemotherapy is unable to induce a permanent second remission. The median survival of these patients is in the range of four to five years from first relapse.33
The concept of chemoimmunotherapy has been evaluated both in rituximab-naïve and rituximab-pre-treated patients. A clear benefit in terms of remission induction, PFS and OS and an additional advantage of maintenance rituximab treatment could be observed when compared with chemotherapy alone.34,35
The implementation of radioimmunotherapy in relapsed/refractory FL produces convincing overall response rates (ORR) ranging from 73 to 83% with tolerable toxicity.36–40
and a trend towards longer time to progression
OS (%) NS
MDS/AML (%) NS
In a randomised trial,
radioimmunotherapy with 90Y-ibritumomab tiuxetan produced a statistically and clinically significant higher ORR and CR compared with rituximab alone,37
(15 versus 10.2 months), duration of response (16.7 versus 11.2 months) and time to next therapy (21.1 versus 13.8 months).39 Moreover, a single dose of 90Y-ibritumomab tiuxetan can produce durable responses and prolonged survival in a substantial number of patients in whom previous therapies have failed.41
Several phase II studies indicated a potential OS/disease-free survival (DFS) benefit of autologous HSCT compared with conventional chemotherapy in patients with recurrent FL.42–47 However, only one multicentre randomised phase III study (the chemotherapy/unpurged autologous/purged autologous [CUP] trial) assessed the role of autologous HSCT in patients with relapsed FL. The results showed a prolonged two-year PFS/four-year OS after autologous HSCT. However, a small patient number (n=89) being randomised to a three-arm study design and short follow-up compromise the reliability of these data.48
In addition, this trial was
performed before the introduction of chemoimmunotherapy regimens, which are now considered to be the treatment of choice in the salvage situation.35
The data for the use of autologous HSCT
are conflicting. In a recently published retrospective analysis of 246 patients who relapsed or had disease progression after initial treatment in the Groupe d'Etude des Lymphomas de l'Adulte (GELA) prospective/randomised trials,28,47
a salvage regimen containing
rituximab with subsequent autologous HSCT led to a dramatic improvement of five-year DFS/OS.49
In contrast, two retrospective analyses and one randomised study found no significant differences EUROPEAN ONCOLOGY
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