By Janet Fricker
At the 13th Haematology Association Meeting (Copenhagen Denmark June 12-15) more than 6,500 delegates braved the perennial Copenhagen hazard of being mown down by a bicycle to hear how haematological cancers are fast becoming chronic conditions.
The meeting highlighted how even multiple myeloma (MM) is being turned into a chronic, manageable disease, due to the efficacy of novel drugs such as thalidomide, lenlidomide and bortezomib. A study by Professor Gareth Morgan and colleagues from the Institute of Cancer Research (London UK) applied new statistical methodology that makes adjustments for patients who cross over to different treatment arms to get an estimation of the true effect of lenalidomide (Revlimid ® ) in addition to dexamethasone, compared to dexamethasone alone on
survival (abstract 0441). Results of the "life time simulation" yielded an estimated mean survival rate of 5.6 life years with the combination treatment, compared to 2.2 life years with dexamethasone alone for patients who had received one prior therapy. "The study reveals extraordinary gains in survival for the combination arm, particularly bearing in mind that these are relapsed/refractory MM patients" commented Professor Brian Durie (Cedars Sinai Medical Centre Los Angeles CA). "The advantage of this technique is that it allows you to get a better handle on treatment outcomes without having to wait 5 to 10 years for survival data."
Although drug innovations may be making significant gains they can be limited by weaknesses in monitoring systems. The 'Best to Test Survey' presented at the meeting revealed that 47 % of the 550 haematologists and oncologists questioned from 11 European countries do not adhere to the European LeukemiaNet recommendations on molecular testing for chronic myeloid leukemia (CML). Guidelines advise quantitative PCR for routine monitoring every three months but the survey showed that 39 % of CML patients across Europe are currently inadequately monitored.
Tyrosine kinase inhibitors (TKIs) first introduced in 2001 have revolutionised CML treatment but resistance to the first line treatment with imatinib occurs in approximately 25 % of chronic phase CML patients, 41 % of accelerated phase patients and 92 % of blast crisis patients.
Monitoring for treatment efficacy at regular intervals helps to determine whether current therapeutic interventions are effectively controlling CML and whether patients might benefit from alternative interventions such as second generation TKIs. "When patients fail therapy their leukaemic burden rises from a few cells to millions of cells and this increases their risk of transformation to blast crisis. If patients aren't monitored regularly you miss out on the small window of opportunity to effectively intervene with alternative therapies" explains Professor Agnes Buzyn (Necker-Enfants Malades Hospital Paris France).
On the subject of TKIs there is increasing evidence that high dose versus standard dose produces a trend towards an improvement in achieving major molecular response . In the Tyrosine kinase inhibition Optimisation and Selectivity (TOPS) trial Jorge Cortes (Anderson Cancer Center Houston Texas) compared the effect of high-dose imatinib (Gleevec) 400 mg BID versus the standard dose of imatinib 400 mg QD in 476 patients with newly diagnosed previously untreated CML (Abstract 402). Results of the first interim analysis show that at 6 months there was a significantly higher rate of complete cytogenetic response with the higher dose (57% versus 45% P=0.0146). "Increasing the doses can speed up the achievement of response and this may possibly translate into a better long-term survival and disease free duration for patients" said Cortes. "I am not sure that similar advantages will be seen with doubling the dose of second generations TKIs since they are already so much more potent."
Other studies illustrated the growing movement in haematological cancers for treatments to be tailored to individuals to avoid unnecessary side effects.
Andrea Gallamini from Azienda Ospedaliera S. Croce (Cuneo Italy) presented a study showing how positron emission tomography (PET) can be used in patients with Hodgkin's lymphoma to identify the patients who can be spared aggressive treatment.
The results showed that for the 50 patients found to be PET scan positive for HL at the interim analysis 43 (86%) showed treatment failure (progression/relapse) by the end of 3.5 years. But of the 210 patients found to be PET scan negative for HL at the interim analysis 199 (95%) showed no progression or relapse by
3.5 years. "On the basis of these results new trials are ongoing worldwide with risk-adapted therapy tailored to individual patients" Dr Gallamini said. "It means that as many as 80 % of patients may be spared the unacceptable toxicity of more aggressive chemotherapy regimens."