1 00:00:00,040 --> 00:00:04,440 These guidelines today have much more clinical trial based 2 00:00:04,440 --> 00:00:09,400 evidence than guidelines from 10 years ago, even if it is a rare 3 00:00:09,400 --> 00:00:12,360 disease. And we have introduced in the 4 00:00:12,360 --> 00:00:17,880 first line a more refined application of standard tools 5 00:00:17,880 --> 00:00:25,400 that existed so far. Welcome to EHA Unplugged, the 6 00:00:25,400 --> 00:00:27,920 official podcast channel from the European Hematology 7 00:00:27,920 --> 00:00:30,840 Association EHA. I'm your host, Isabella Olivera. 8 00:00:31,680 --> 00:00:35,880 Today we're talking about the recent ESMO EHA guidelines for 9 00:00:36,000 --> 00:00:38,880 peripheral T and natural killer cell lymphomas. 10 00:00:39,360 --> 00:00:42,000 This is a collaboration between ESMO and EHA. 11 00:00:42,120 --> 00:00:44,840 To walk us through these wide lines, we have today 2 12 00:00:44,840 --> 00:00:48,680 professors, Francesco Lamore from ESMO and Massimo Federico 13 00:00:48,680 --> 00:00:51,840 from EHA. Professor Damore is a clinical 14 00:00:51,840 --> 00:00:55,280 professor and chair of the Department of Hematology at Arus 15 00:00:55,280 --> 00:00:58,120 University in Denmark. And Professor Massimo Federico 16 00:00:58,200 --> 00:01:01,440 is a senior professor of medical oncology at the University of 17 00:01:01,440 --> 00:01:04,879 Modena and Radio Media in Italy. They were both deeply involved 18 00:01:04,879 --> 00:01:07,360 in shaping these guidelines, and they're here to help us 19 00:01:07,360 --> 00:01:10,360 understand what's new in these guidelines, why these changes 20 00:01:10,360 --> 00:01:13,160 matter, and how they can make a difference for patients. 21 00:01:13,680 --> 00:01:15,400 Thank you for being with us today. 22 00:01:16,080 --> 00:01:20,120 Thank you for your invitation. Thank you for invitation. 23 00:01:20,560 --> 00:01:24,280 We're going to start by clarifying which informants are 24 00:01:24,320 --> 00:01:28,600 in this guideline that uses the term PTCL to cover malignancies 25 00:01:28,600 --> 00:01:31,400 that are derived from either T or NK cells. 26 00:01:31,760 --> 00:01:34,800 There are many two types what is covered in this guideline. 27 00:01:35,120 --> 00:01:39,320 These guidelines cover the different peripheral T cell 28 00:01:39,560 --> 00:01:44,760 lymphomas that are classified as a nodal, extra nodal, and 29 00:01:44,800 --> 00:01:50,600 leukemic disseminated. We did not cover the topics of 30 00:01:50,840 --> 00:01:53,200 cutaneous peripheral T cell lymphoma. 31 00:01:53,480 --> 00:01:58,520 We did not cover the pretymic either, that is the T cell 32 00:01:58,520 --> 00:02:01,920 derived acute lymphoblastic leukemias and lymphoblastic 33 00:02:01,920 --> 00:02:05,240 lymphomas. So it is the mature entities, 34 00:02:05,640 --> 00:02:10,199 postymic with the exclusion, as Professor Federico just said, of 35 00:02:10,199 --> 00:02:13,200 the cutaneous one among the mature entities. 36 00:02:14,800 --> 00:02:17,520 And why was there a need for this new guidelines? 37 00:02:18,120 --> 00:02:22,520 The last guidelines were that the community received in this 38 00:02:22,520 --> 00:02:28,120 context were produced in 2015. A decade ago landscape of 39 00:02:28,120 --> 00:02:34,560 peripheral T cell lymphomas, T&K cell lymphomas was significantly 40 00:02:35,320 --> 00:02:38,760 more simple. But there has been an increase, 41 00:02:38,760 --> 00:02:45,960 a dramatic increase in complexity due to steep growth 42 00:02:46,200 --> 00:02:50,120 of knowledge in the in these entities, knowledge about their 43 00:02:50,120 --> 00:02:54,800 biology, which also has led to the definition of new entities. 44 00:02:54,800 --> 00:02:58,160 As we take for example, the breast implant associated 45 00:02:58,440 --> 00:03:02,560 anaplastic glass cell informer was something absolutely absent 46 00:03:02,560 --> 00:03:06,080 in the latest guidelines. In the latest guidelines we were 47 00:03:06,080 --> 00:03:11,000 talking about intestinal T cell informers that were enteropathy 48 00:03:11,000 --> 00:03:15,960 associated type 2 which we called it enteropathy associated 49 00:03:15,960 --> 00:03:17,880 but there was no enteropathy around. 50 00:03:18,120 --> 00:03:22,280 Today this has changed the name and has also completely 51 00:03:22,360 --> 00:03:28,080 different biology and background from the well known and celiac 52 00:03:28,080 --> 00:03:30,000 disease associated T cell informers. 53 00:03:30,000 --> 00:03:33,200 These are two examples of brand new things, and there are many 54 00:03:33,200 --> 00:03:37,800 more to to mention that make the complexity level of these 55 00:03:37,800 --> 00:03:42,560 guidelines much more difficult to see and to understand if you 56 00:03:42,680 --> 00:03:45,800 if you don't have specific guidelines looking at all the 57 00:03:45,800 --> 00:03:48,600 entities. In addition to the clarification 58 00:03:48,880 --> 00:03:53,000 of Professor Damore, I would like to also underline that we 59 00:03:53,040 --> 00:04:00,160 did our best to offer practical deadlines for more than a dozen 60 00:04:00,200 --> 00:04:04,720 of different subtypes just to help physicians to find 61 00:04:04,720 --> 00:04:09,240 correctly the deadlines for the specific, for the single 62 00:04:09,240 --> 00:04:12,360 patients. So it was really a huge effort 63 00:04:12,360 --> 00:04:15,960 to not to offer detailed information on how to treat 64 00:04:16,040 --> 00:04:20,399 nodal, different types of nodal extranodal, different types of 65 00:04:20,399 --> 00:04:23,920 extranodal and so on. And this was one of the most 66 00:04:23,920 --> 00:04:26,920 relevant reasons for the need of an update. 67 00:04:28,360 --> 00:04:32,080 The first program I imagine is to diagnose this lymphomas 68 00:04:32,160 --> 00:04:34,800 because there are so many subtypes and they are rare. 69 00:04:35,760 --> 00:04:38,400 How to diagnose today? What are the recommendations in 70 00:04:38,400 --> 00:04:41,000 this guideline? To begin with, as the answer of 71 00:04:41,000 --> 00:04:43,360 this question to this question, we have one of the most 72 00:04:43,360 --> 00:04:47,040 recognized T cell lymphoma pathologist as a member of our 73 00:04:47,440 --> 00:04:51,960 author group, Professor de la Belle that has produced quite 74 00:04:54,240 --> 00:04:57,840 detailed overviews and algorithms for the diagnosis 75 00:04:58,040 --> 00:05:02,840 which is based on a three level tire diagnostic approach. 76 00:05:03,200 --> 00:05:06,640 The first level is the morphology, the second level is 77 00:05:06,640 --> 00:05:09,000 the immunohistochemistry as we are used. 78 00:05:09,000 --> 00:05:13,600 But then there is 1/3 tire which is the molecular profiling at 79 00:05:13,600 --> 00:05:19,720 genomic level which today has entered the diagnostic area no 80 00:05:19,720 --> 00:05:25,240 longer as a research topic but more and more interacting with 81 00:05:25,240 --> 00:05:29,960 the daily diagnostic decisions. So the genomic profile for 82 00:05:29,960 --> 00:05:35,400 example in TFH particular helper T cell derived lymphomas will 83 00:05:35,400 --> 00:05:39,840 allow you to make decisions in the in the first line and 84 00:05:39,840 --> 00:05:45,120 relapse, relapse setting for example, for the use of hyper 85 00:05:45,120 --> 00:05:49,200 methylating agents that are no no longer only for research, but 86 00:05:49,200 --> 00:05:51,840 also introduced in the daily practice today. 87 00:05:52,520 --> 00:05:54,880 So these are new things that they got the guidelines from 88 00:05:54,880 --> 00:06:01,000 2015 did not have at all. And so I would also add that we 89 00:06:01,000 --> 00:06:06,120 did our best that we tried also to clarify the complexity, 90 00:06:06,520 --> 00:06:10,880 complexity of the initial diagnosis for the needs for 91 00:06:10,880 --> 00:06:16,280 confirmation by an expert pathologist and also the need to 92 00:06:16,280 --> 00:06:21,160 have a multidisciplinary approach in planning right to 93 00:06:21,160 --> 00:06:24,840 treatment according to the subtypes and the extension of 94 00:06:24,840 --> 00:06:27,800 the disease. But also we would like to help 95 00:06:27,800 --> 00:06:31,960 physicians to treat their patients in the area of 96 00:06:31,960 --> 00:06:35,080 residency of the patients. So it's a rare disease. 97 00:06:35,600 --> 00:06:39,440 Now it is impossible to imagine that we can cover with the 98 00:06:39,600 --> 00:06:45,080 referral center everywhere. So we we have to also to try to 99 00:06:45,080 --> 00:06:49,720 combine the the needs for a correct diagnosis and the needs 100 00:06:49,720 --> 00:06:55,080 for the treatment not so far from the area of residency of 101 00:06:55,080 --> 00:06:58,760 the patients. And this is an effort of of the 102 00:06:58,760 --> 00:07:01,880 group to clarify what is essential. 103 00:07:01,920 --> 00:07:06,160 First level, second level, third level, the need for discussing 104 00:07:06,200 --> 00:07:11,320 the diagnosis, the suspected diagnosis at the referral level 105 00:07:11,640 --> 00:07:15,760 and then offered the opportunity to treat the patients as close 106 00:07:15,760 --> 00:07:20,520 as possible to their residency. So it is not so easy, but so 107 00:07:20,800 --> 00:07:24,560 we're trying to do this. But it's not something that the 108 00:07:24,560 --> 00:07:29,880 guidelines can go and, and organize in the, in the text 109 00:07:29,880 --> 00:07:33,360 because there is such a heterogeneity of realities out 110 00:07:33,360 --> 00:07:35,560 there. And these are guidelines that 111 00:07:35,560 --> 00:07:38,760 are, that are read across the world of global guidelines. 112 00:07:38,760 --> 00:07:42,280 Although they're European in origin, they will be, they will 113 00:07:42,280 --> 00:07:47,360 be read in the, in the Americas, in Asia, in global fashion. 114 00:07:47,560 --> 00:07:50,520 So it's difficult to come and organize things that are 115 00:07:50,720 --> 00:07:54,840 extremely heterogeneous. It is a rare disease, it is a 116 00:07:54,840 --> 00:07:57,160 difficult disease even for experts. 117 00:07:57,400 --> 00:08:02,040 And if you have to be treated firstly, diagnosed correctly and 118 00:08:02,040 --> 00:08:06,520 then treated, it is important that, as the professor said, 119 00:08:06,520 --> 00:08:10,760 Federico said, it is important that a person with experience is 120 00:08:10,760 --> 00:08:13,640 looking at these things and a group, A-Team, a 121 00:08:13,640 --> 00:08:17,360 multidisciplinary team, where it is possible to have it, is there 122 00:08:17,360 --> 00:08:22,160 because that offers the patient the possibility of survival, 123 00:08:22,160 --> 00:08:25,200 which is significantly higher than if you're treated standard 124 00:08:25,200 --> 00:08:27,880 of care in some kind of discipline, viable environment. 125 00:08:28,320 --> 00:08:31,840 So with respect, with the difference, huge difference that 126 00:08:31,840 --> 00:08:35,280 there is not only in countries, but areas of the world, this 127 00:08:35,280 --> 00:08:38,960 must be said about these diseases because they, they are, 128 00:08:39,520 --> 00:08:42,840 they are very difficult. We we had recently a meeting in 129 00:08:42,840 --> 00:08:44,880 Asia. In different countries it's 130 00:08:44,880 --> 00:08:49,160 extremely different how diagnostic and interpretation is 131 00:08:49,160 --> 00:08:51,240 depending on the region you're taught talking about. 132 00:08:52,320 --> 00:08:56,880 So the first the big challenge is diagnosis, but then can you 133 00:08:56,880 --> 00:09:00,880 summarize how these guidelines approach the treatment in first 134 00:09:00,880 --> 00:09:03,160 line? Which are the main points you 135 00:09:03,160 --> 00:09:08,960 want to highlight? Yes, the, the, the first line is 136 00:09:09,040 --> 00:09:12,360 of course something that needs as much evidence as possible. 137 00:09:12,400 --> 00:09:15,320 We are, we work in these guidelines with levels of 138 00:09:15,360 --> 00:09:19,880 evidence and in, in the, in the recognized international 139 00:09:19,920 --> 00:09:22,920 terminology. And as you can imagine in 140 00:09:22,920 --> 00:09:26,840 diseases that are rare, there will never be the big trials 141 00:09:26,840 --> 00:09:30,480 with hundreds or thousands of patients like you have in some 142 00:09:30,480 --> 00:09:35,080 other some other sections of oncology like breast cancer, 143 00:09:35,280 --> 00:09:37,400 colon cancer. This is a rare disease. 144 00:09:37,400 --> 00:09:41,040 So there will be small trials. The evidence will be relatively 145 00:09:41,040 --> 00:09:43,040 weak and we have to work with that. 146 00:09:43,040 --> 00:09:47,920 But these guidelines today have much more clinical trial based 147 00:09:47,920 --> 00:09:52,840 evidence than guidelines from 10 years ago, even if it is a rare 148 00:09:52,840 --> 00:09:55,840 disease. And we have introduced in the 149 00:09:55,840 --> 00:10:01,600 first line a more refined application of standard tools 150 00:10:01,600 --> 00:10:05,440 that existed so far. The use, for example, of a 151 00:10:06,240 --> 00:10:09,640 chopped backbone CHOP is an abbreviation for 152 00:10:09,920 --> 00:10:13,720 cyclophosphamide, hydroxydonor, rubicine, vincristine and 153 00:10:13,720 --> 00:10:17,680 Prednisolone, with or without the addition of a topocyte, with 154 00:10:17,680 --> 00:10:22,200 or without the use of a stem cell cell transplant of some 155 00:10:22,200 --> 00:10:26,240 kind, autologous or allogeneic. But these things were also 156 00:10:26,240 --> 00:10:30,640 mentioned in decade ago. What is different is that it is 157 00:10:30,640 --> 00:10:35,840 a refined mentioning based on recent clinical trials, based 158 00:10:35,840 --> 00:10:41,000 also on world evidence from registries, population base and 159 00:10:41,040 --> 00:10:43,680 also from experience with long term follow up. 160 00:10:43,960 --> 00:10:48,360 So this refinement is something that we didn't have in the past. 161 00:10:48,360 --> 00:10:51,040 We have looked at for example a toposite has been a long 162 00:10:51,040 --> 00:10:54,840 discussion in the community. But the, the guidelines now say, 163 00:10:55,120 --> 00:11:00,400 we know that a toposite has time after time shown an effect in 164 00:11:00,560 --> 00:11:04,920 elk positive ALCL. It it has been shown in 165 00:11:04,920 --> 00:11:08,600 prospective trials and it has been shown in several 166 00:11:08,600 --> 00:11:12,920 retrospective analysis. So you can, you can say that the 167 00:11:12,920 --> 00:11:18,880 use of a topazide in elk positive ALCL is not just at the 168 00:11:18,880 --> 00:11:21,080 same level as the other entities. 169 00:11:21,160 --> 00:11:25,600 Elk positive ALCL seem to have a predilection, seems to have a 170 00:11:25,600 --> 00:11:29,760 specifically good response compared to the other entities. 171 00:11:29,920 --> 00:11:33,480 So this is what I mean by refinement of what we told 172 00:11:33,720 --> 00:11:38,760 people 10 years ago. In first line therapy, what we 173 00:11:38,760 --> 00:11:43,960 clearly tried to do is to offer the opportunity to select the 174 00:11:43,960 --> 00:11:48,120 right management, the right approach according to stage of 175 00:11:48,120 --> 00:11:50,640 the disease and histologic subtype. 176 00:11:51,560 --> 00:11:57,800 And when is better to use CHOP, CHOP, eat a chopper plus a 177 00:11:57,800 --> 00:12:02,040 topocide. When adding novel agents like 178 00:12:02,120 --> 00:12:07,680 brintuximabedotin in anaplastic large cell lymphoma setting. 179 00:12:08,040 --> 00:12:11,800 And also the the more appropriate approach for 180 00:12:11,800 --> 00:12:15,840 offering a stem cell transplant at the end of induction therapy 181 00:12:16,080 --> 00:12:20,360 in those entities where it is clear that this could be of 182 00:12:20,360 --> 00:12:22,680 benefit. Although we are still lacking 183 00:12:22,960 --> 00:12:25,400 prospective randomized at the clinical trial. 184 00:12:25,760 --> 00:12:29,480 So just for summarizing this aspect of first line therapy, 185 00:12:29,840 --> 00:12:34,760 first the panel suggests to consider patients for enrollment 186 00:12:34,760 --> 00:12:39,000 in clinical trial. Second, in terms of standard 187 00:12:39,120 --> 00:12:44,120 care, those people that like to check for our deadlines have 188 00:12:44,160 --> 00:12:50,040 three figures to summarizing the flow chart for patients with 189 00:12:50,040 --> 00:12:53,480 nodal extranodal and low clinic disease. 190 00:12:53,640 --> 00:12:58,360 So we hope for a lot of opportunities to try to find the 191 00:12:58,360 --> 00:13:02,800 right place for selecting treatment for the patient. 192 00:13:03,240 --> 00:13:08,160 So just to just to, just to mention on the on the transplant 193 00:13:08,160 --> 00:13:12,880 have we have the trials that have been published one year ago 194 00:13:12,880 --> 00:13:18,440 2024 showing for example the randomized trial run in France 195 00:13:18,440 --> 00:13:25,160 and Germany, the AATT trial published in 2021 in blood and 196 00:13:25,160 --> 00:13:28,880 then again now in 2024 with a long term follow up. 197 00:13:29,400 --> 00:13:35,320 This information with a with a comparison between autologous 198 00:13:35,320 --> 00:13:39,360 and allogeneic transplant in the front line setting was an 199 00:13:39,360 --> 00:13:43,680 important information for the community because you you could 200 00:13:43,680 --> 00:13:48,400 see and confirmed in both the final analysis of 21 and the 201 00:13:48,400 --> 00:13:54,720 long term follow up of 24 that what you gain in terms of better 202 00:13:55,360 --> 00:13:59,600 duration of response with a Nello transplant in. 203 00:13:59,760 --> 00:14:04,600 In other words, less relapses, lymphoma related relapses you 204 00:14:04,600 --> 00:14:08,400 lose on in term of transplant related mortality. 205 00:14:08,800 --> 00:14:13,440 So there is a toxicity from the modality which has less relapses 206 00:14:13,440 --> 00:14:16,800 at at the end of the day, they balance each other completely. 207 00:14:16,960 --> 00:14:20,720 So there is no difference. So this information is important 208 00:14:20,720 --> 00:14:24,120 for the community. And this is another example of 209 00:14:24,600 --> 00:14:28,880 applying things at at the right time, the right thing at the 210 00:14:28,880 --> 00:14:32,440 right time. The guideline ends up if you, if 211 00:14:32,440 --> 00:14:35,920 you have a transplant eligible patient saying, well transplant 212 00:14:35,920 --> 00:14:40,040 should be autologous in the upfront setting where you don't 213 00:14:40,080 --> 00:14:44,120 where you still have the LO option in the relapse setting to 214 00:14:44,120 --> 00:14:46,960 salvage your patient if the patient relapses. 215 00:14:47,400 --> 00:14:51,720 So this isn't quite important message from from the guideline, 216 00:14:51,880 --> 00:14:56,120 which is sustained not just by a gut feeling, but by a randomized 217 00:14:56,120 --> 00:14:59,240 trial that has been published in the Journal of Clinical Oncology 218 00:14:59,560 --> 00:15:03,200 just 12 months ago. Is there anything you would like 219 00:15:03,200 --> 00:15:05,720 to highlight about the second line so the relapse? 220 00:15:05,720 --> 00:15:06,600 Setting. Yes. 221 00:15:06,600 --> 00:15:11,720 So we started the from the the knowledge that so far the 222 00:15:11,960 --> 00:15:15,640 outcome of patients with refractory or relapsed 223 00:15:16,000 --> 00:15:18,400 peripheral tisel lymphoma is usually dismal. 224 00:15:18,560 --> 00:15:22,680 So there is a need for improvement and the deadlines 225 00:15:22,760 --> 00:15:28,680 also offer the best evidence on the new agents that have to be 226 00:15:28,680 --> 00:15:33,760 considered for patients with relapsed or refractory disease 227 00:15:34,120 --> 00:15:38,520 together with the best use of Autolu stem cell transplant and 228 00:15:38,520 --> 00:15:42,720 also other innovative approach. But probably professor for the 229 00:15:42,720 --> 00:15:48,120 more already can just underline some specific benefit of new 230 00:15:48,120 --> 00:15:52,600 agency in specific subtypes of relapse of the T cell lymphoma. 231 00:15:53,240 --> 00:15:57,080 I want to just wrap up on around the approach of the stem cell 232 00:15:57,080 --> 00:15:59,360 transplant that in the guidelines you will see 233 00:15:59,360 --> 00:16:02,920 autologous transplant applied to frontline approach with some 234 00:16:02,920 --> 00:16:06,960 notable exception exceptions For example, the hepatosplenic T 235 00:16:06,960 --> 00:16:13,080 cell Informa and the monomorphic epitheliotropic intestinal T 236 00:16:13,080 --> 00:16:15,600 cell Informa. The Michael, those two we 237 00:16:15,600 --> 00:16:20,360 recommend allogeneic upfront otherwise most of the others 238 00:16:20,680 --> 00:16:26,120 nodal and externodal will be would be the recommendation of 239 00:16:26,120 --> 00:16:28,520 photologists. Whereas in the relapse setting 240 00:16:28,600 --> 00:16:32,640 all chemosensitive patients that are transplant eligible are 241 00:16:32,640 --> 00:16:35,680 recommended treated by allogeneic transplant. 242 00:16:36,000 --> 00:16:41,160 This is a major pattern and for the leukemic entities that we 243 00:16:41,160 --> 00:16:44,160 have in these guidelines, we didn't have them ten years ago. 244 00:16:44,560 --> 00:16:48,880 If they are chemosensitive in the three aggressive entities, 245 00:16:49,040 --> 00:16:53,720 then we recommend to treat them or consolidate them with 246 00:16:53,880 --> 00:16:56,840 allogeneic transplant in the relapse setting. 247 00:16:56,840 --> 00:17:02,600 One comment is also a new trend surging significantly in the 248 00:17:02,640 --> 00:17:06,760 field of T cell informers of the importance of minimal residual 249 00:17:06,760 --> 00:17:09,200 disease. We know minimal residual disease 250 00:17:09,200 --> 00:17:13,040 from leukemia, we know it from mental cell Informa, We know it 251 00:17:13,040 --> 00:17:16,040 even for a diffuse large B cell Informa. 252 00:17:16,040 --> 00:17:20,720 It is a topic that is more and more usual in these discussions. 253 00:17:20,720 --> 00:17:24,839 But for T cell entities, it has been a challenge also in this 254 00:17:24,839 --> 00:17:28,800 field because the T cell receptor rearrangement clone 255 00:17:28,800 --> 00:17:31,720 clonality has not been easy to demonstrate. 256 00:17:32,320 --> 00:17:37,840 But today the tool of circulating T circulating tumor 257 00:17:37,920 --> 00:17:44,160 DNA, CT DNA really taking speed and, and and and increasing in 258 00:17:44,240 --> 00:17:47,360 publications. I just came home from from a 259 00:17:47,360 --> 00:17:50,600 meeting a few days ago. There was a huge publication 260 00:17:50,640 --> 00:17:54,440 that shows patients we call incomplete remission with 261 00:17:54,440 --> 00:17:58,960 standard of care tools today, which is the PET CT scanning 262 00:17:59,040 --> 00:18:03,400 metabolic complete remission. Almost half of them that are 263 00:18:03,400 --> 00:18:08,960 called CRS by PET CT, they still have minimal as usual disease if 264 00:18:08,960 --> 00:18:15,120 you if you look at it with MRD. So actually in shop only treated 265 00:18:15,120 --> 00:18:20,480 PTCL in that publication at the end of the day, 29% of the 266 00:18:20,480 --> 00:18:25,680 patients treated had MRD negative status at the end of 267 00:18:25,680 --> 00:18:28,760 the treatment. So what I'm saying is we will 268 00:18:28,760 --> 00:18:32,720 learn in time already, not in time, but it's already there. 269 00:18:32,720 --> 00:18:38,320 It's already now we will learn that MRD will give us new way of 270 00:18:38,320 --> 00:18:42,160 approaching the disease because what we have been calling CR 271 00:18:42,160 --> 00:18:46,720 until now is maybe not CR. Is this already in the 272 00:18:46,760 --> 00:18:48,040 guideline? The MRDN. 273 00:18:48,720 --> 00:18:53,840 We just mentioned it, but CT DNA will be one of the two topics in 274 00:18:53,960 --> 00:18:57,280 my opinion, that will dominate the update of the next 275 00:18:57,280 --> 00:19:00,720 guideline. If you, if you ask me what, 276 00:19:00,920 --> 00:19:04,640 what, what will happen for in the next guideline? 277 00:19:05,000 --> 00:19:10,600 What do you expect to be the new hot topics in the next 278 00:19:10,720 --> 00:19:13,280 guidelines? And of course, in guidelines, 279 00:19:13,280 --> 00:19:17,080 you cannot have publications that are so recent that you 280 00:19:17,080 --> 00:19:20,400 need, you need more confirmation, you need third 281 00:19:20,400 --> 00:19:23,440 publication that shows the same. So it takes a little bit of 282 00:19:23,440 --> 00:19:25,680 time. Guidelines will always be a 283 00:19:25,680 --> 00:19:30,040 little bit the breaking news of of of the field, but I think the 284 00:19:30,040 --> 00:19:32,680 next guideline will contain it so. 285 00:19:33,560 --> 00:19:35,720 There's this concept of living guideline. 286 00:19:36,760 --> 00:19:39,120 Yes, yeah, it is. It is necessary. 287 00:19:39,120 --> 00:19:43,000 Otherwise, you know, they become like dinosaurs, they become like 288 00:19:43,000 --> 00:19:48,440 some some stone in past, which is very interesting to see from 289 00:19:48,440 --> 00:19:51,760 an archaeological point of view. But if you if you have to work 290 00:19:52,040 --> 00:19:55,240 with that every day in your clinic, then you would like to 291 00:19:55,240 --> 00:19:59,120 have something more living. And the NCCN has done that. 292 00:19:59,320 --> 00:20:04,320 We try to do the same. Exactly 1 of the aims of this 293 00:20:04,320 --> 00:20:10,800 group of people supported by ESMA is to update guidelines as 294 00:20:10,800 --> 00:20:14,800 timely as possible. I don't know if we will be able 295 00:20:14,800 --> 00:20:19,160 to do twice the year or three times per year or once in two 296 00:20:19,160 --> 00:20:22,000 years. However, once we will have 297 00:20:22,480 --> 00:20:27,200 relevant information coming from research being the clinical 298 00:20:27,200 --> 00:20:33,080 trials or other biological news. Of course, Francesco and all the 299 00:20:33,080 --> 00:20:37,000 group is in agreement with the discuss the opportunity to 300 00:20:37,000 --> 00:20:41,680 create an update or to inform the community that there are 301 00:20:41,680 --> 00:20:45,480 news compared to the already released deadlines. 302 00:20:45,680 --> 00:20:49,320 This is very important it. Must be also easier by the 303 00:20:49,320 --> 00:20:53,000 collaboration between ESMO and EHA to keep updating this 304 00:20:53,000 --> 00:20:56,800 guidance to join the airports. It's good that societies, 305 00:20:56,800 --> 00:21:00,600 European societies show they can work together and we, I mean, it 306 00:21:00,600 --> 00:21:02,320 is the first time in T cell informers. 307 00:21:02,320 --> 00:21:05,680 But if you look at myeloma, they're just being published the 308 00:21:05,680 --> 00:21:10,120 ESMO AI myeloma guideline, common guideline. 309 00:21:10,320 --> 00:21:15,360 So there are good examples and other that are continuously 310 00:21:15,400 --> 00:21:17,840 produced. Get back to your question about 311 00:21:17,880 --> 00:21:20,560 about refractory, relapsed refractory disease. 312 00:21:20,560 --> 00:21:24,920 The guidelines also have caught some of the very, very new 313 00:21:24,920 --> 00:21:29,720 publications about novel drugs that have been clinical trial 314 00:21:29,720 --> 00:21:33,320 based. And just to anecdotally for this 315 00:21:33,320 --> 00:21:38,160 podcast, I can tell you we got the results of the clinical 316 00:21:38,160 --> 00:21:43,880 trial, the SPIRIT trials by the professor of Chai that published 317 00:21:43,880 --> 00:21:47,840 that in Lensity Hematology in the summer of 2000 and it 318 00:21:47,840 --> 00:21:51,440 appeared in Density Hematology. Actually I think it was one week 319 00:21:51,520 --> 00:21:55,000 or two weeks before we had to send the manuscript out in 320 00:21:55,000 --> 00:21:57,880 external review and and we sat in the group. 321 00:21:57,880 --> 00:22:01,040 Well, we would like to have this publication mentioned. 322 00:22:01,120 --> 00:22:04,880 So it was very last second. We caught that bus and put and 323 00:22:04,880 --> 00:22:07,520 put that publication in our references. 324 00:22:07,520 --> 00:22:12,600 And it is a treatment of external NKT lymphoma that is a 325 00:22:12,600 --> 00:22:16,880 typical nasal type lymphoma present in Europe but more 326 00:22:16,880 --> 00:22:22,520 frequent in Asia where the use of checkpoint inhibitor, which 327 00:22:22,520 --> 00:22:26,840 is a novel drug in the context of NKT lymphoma. 328 00:22:27,040 --> 00:22:33,040 But it has unique favorable effect combined with the usual 329 00:22:33,040 --> 00:22:36,080 Aspergenase containing regiments. 330 00:22:36,480 --> 00:22:40,040 So if you add upfront, actually this trial was upfront first 331 00:22:40,040 --> 00:22:44,640 line, it came on top of results that we already had in small 332 00:22:44,640 --> 00:22:46,600 phase two trials in the relapse setting. 333 00:22:46,840 --> 00:22:51,480 But this upfront trial with overall response rate of almost 334 00:22:51,480 --> 00:22:56,800 80% that that has been completely new in the field. 335 00:22:57,200 --> 00:23:00,880 So I'm very happy and a little bit proud that we had this 336 00:23:00,880 --> 00:23:06,720 publication included at the last minute in the in these in these 337 00:23:06,720 --> 00:23:09,800 guidelines. So Professor Federico, what 338 00:23:09,800 --> 00:23:12,080 would be your take away message for the audience? 339 00:23:12,480 --> 00:23:15,880 The the most important recommendation in my view is one 340 00:23:15,880 --> 00:23:19,520 of you suspect to have a patients with peripheral test 341 00:23:19,520 --> 00:23:23,280 cell lymphoma. Please check for a correct 342 00:23:23,320 --> 00:23:26,560 diagnosis. This is first, if you are not 343 00:23:26,560 --> 00:23:31,040 all the facilities in your area, please connect with the centers 344 00:23:31,040 --> 00:23:38,640 that can help you in confirming or not confirming the diagnosis. 345 00:23:38,640 --> 00:23:42,920 This is the first step. Now correct diagnosis will 346 00:23:42,920 --> 00:23:47,280 translate in the best opportunity to offer the right 347 00:23:47,600 --> 00:23:50,680 treatment and the best options for cure. 348 00:23:51,360 --> 00:23:54,680 So the second is if you have a patients with a confirmed 349 00:23:54,680 --> 00:23:58,240 diagnosis of peripheral lymphoma, consider the 350 00:23:58,240 --> 00:24:00,920 opportunity to enroll the patients in a clinical trial. 351 00:24:02,160 --> 00:24:06,400 Third, if you have to offer just a standard care, please follow 352 00:24:06,480 --> 00:24:09,600 the deadlines. We have recently released that, 353 00:24:09,760 --> 00:24:14,360 in my opinion, they have one of the most relevant efforts to 354 00:24:14,800 --> 00:24:18,920 help physicians to make the right decision for the patients. 355 00:24:20,080 --> 00:24:22,880 And I asked the same question to you, Professor Amore, what would 356 00:24:22,880 --> 00:24:27,040 be for you the take away message for everybody to go and read 357 00:24:27,040 --> 00:24:28,880 this guideline? Because it's a very complex 358 00:24:29,440 --> 00:24:31,600 subject, we cannot cover the whole thing in. 359 00:24:32,520 --> 00:24:37,160 I would say to the to the reader of the guideline, the 360 00:24:37,160 --> 00:24:42,840 recommendation how to read the guideline is Please. 361 00:24:42,840 --> 00:24:46,640 If you mean it seriously, then read the guideline in its 362 00:24:46,640 --> 00:24:49,600 entirety. Read the main manuscript, but 363 00:24:49,600 --> 00:24:52,080 read also the supplementary of the guideline. 364 00:24:52,240 --> 00:24:56,760 The supplementary is only supplementary because there is a 365 00:24:56,760 --> 00:24:59,440 limit of words from the journals. 366 00:25:00,160 --> 00:25:02,920 The things in the supplementary are important things, 367 00:25:03,480 --> 00:25:07,560 particularly in T cell lymphomas where we have so many entities 368 00:25:07,560 --> 00:25:11,080 and particularly the very rare entities that many physicians 369 00:25:11,080 --> 00:25:15,520 feel a little bit shaky about because they maybe have not seen 370 00:25:15,640 --> 00:25:18,680 such a patient ever. So my recommendation is please 371 00:25:18,680 --> 00:25:22,800 read the entire guideline. In my opinion, you have not read 372 00:25:22,800 --> 00:25:26,240 the guideline if you don't read both the main manuscript and the 373 00:25:26,240 --> 00:25:31,000 supplementary as a recommendation for what to do to 374 00:25:31,000 --> 00:25:34,000 your pace to your patient with preferred T cell informers. 375 00:25:34,200 --> 00:25:38,240 As as it was said by Massimo, by Professor Federico, the the 376 00:25:38,360 --> 00:25:42,760 importance of trying to put patient in a clinical trial is 377 00:25:42,760 --> 00:25:46,760 just because what happens in a clinical trial is that you have 378 00:25:46,760 --> 00:25:49,600 more precision about what's going on. 379 00:25:49,680 --> 00:25:53,520 You gather information, you have a monitoring of your patients 380 00:25:54,040 --> 00:25:56,160 and those that have looked at it. 381 00:25:56,160 --> 00:26:00,520 There are some interesting, interesting studies done on plus 382 00:26:00,520 --> 00:26:03,680 minus clinical trial within a certain disease. 383 00:26:04,120 --> 00:26:08,560 And there is a difference in in survival, not because the 384 00:26:08,560 --> 00:26:11,120 clinical trial was the best clinical trial in the world, but 385 00:26:11,200 --> 00:26:15,400 the fact that the patient is monitored and is carefully 386 00:26:15,400 --> 00:26:20,200 followed that makes it less likely to have complications 387 00:26:20,640 --> 00:26:26,200 that come maybe suddenly without anybody expecting it and also a 388 00:26:26,200 --> 00:26:30,360 better care of the patient. So there is an there is an 389 00:26:30,360 --> 00:26:32,680 advantage to have a patient in a clinical trial. 390 00:26:33,400 --> 00:26:37,120 But the problem is and any reader of the guidelines will of 391 00:26:37,120 --> 00:26:41,440 course agree that if there is no clinical trial, which is the 392 00:26:41,440 --> 00:26:45,480 most frequent situation you are in, then the recommendation to 393 00:26:45,760 --> 00:26:48,480 to bring your patient in the clinical trial is not so easy. 394 00:26:49,040 --> 00:26:51,880 And sometimes you can get a clinical trial, you have to send 395 00:26:51,880 --> 00:26:55,480 your patient out of the country and that is also a little bit 396 00:26:55,480 --> 00:26:57,200 heavy for the patient and the family. 397 00:26:57,280 --> 00:26:59,960 But but that, that would be best. 398 00:26:59,960 --> 00:27:04,360 And we have highlighted that in the guidelines and importantly 399 00:27:04,560 --> 00:27:08,920 that disciplines talk together. So it is important to have a 400 00:27:08,920 --> 00:27:12,080 tertiary center. I know there will be different 401 00:27:12,080 --> 00:27:16,400 realities around the world, but this multidisciplinary approach 402 00:27:16,400 --> 00:27:21,280 from pathology in one end to clinical, clinical intervention 403 00:27:21,280 --> 00:27:25,480 in the other end, our treatment will never be better than the 404 00:27:25,480 --> 00:27:29,840 diagnosis we are offered from the from the diagnostic side. 405 00:27:30,040 --> 00:27:34,040 If the diagnosis is wrong, our treatment will be wrong or not 406 00:27:34,040 --> 00:27:38,600 appropriate. So, and I have the impression in 407 00:27:38,600 --> 00:27:42,400 this particular guideline, the first key aspect is really a 408 00:27:42,600 --> 00:27:45,720 correct diagnosis because there are so many entities. 409 00:27:46,240 --> 00:27:50,680 And from what I could see in the guideline also each entity is 410 00:27:50,800 --> 00:27:53,880 treated in a different way, in a slightly different way in any 411 00:27:53,880 --> 00:27:56,520 case. So it's key to go and look at 412 00:27:56,560 --> 00:28:00,920 all the details and be precise. So you know you have a 413 00:28:00,920 --> 00:28:04,440 heterogeneity here which is practically unseen. 414 00:28:04,520 --> 00:28:07,240 I know there are variants in mental cell lymphoma, there are 415 00:28:07,240 --> 00:28:11,040 variants in diffuse large B cell lymphomas, but but these are 416 00:28:11,040 --> 00:28:14,760 biologically completely different diseases. 417 00:28:15,160 --> 00:28:18,880 If you think about the lymphoma arising from a breast implant 418 00:28:19,400 --> 00:28:23,760 and the lymphoma arising from a patient with celiac disease in 419 00:28:23,760 --> 00:28:28,200 the in the small bowel, these two diseases are so far from 420 00:28:28,200 --> 00:28:31,200 each other. OK, they derive from T cell from 421 00:28:31,200 --> 00:28:34,520 T cells, but they are two complete different planets. 422 00:28:35,800 --> 00:28:38,040 So is there anything else you would like to add for the 423 00:28:38,120 --> 00:28:41,600 audience? My wish is to ask the audience 424 00:28:42,080 --> 00:28:47,880 to use the deadlines and in case they need some more explanation, 425 00:28:47,880 --> 00:28:51,880 contact us and we will do our best also to clarify. 426 00:28:53,080 --> 00:28:57,040 And I would say to the audience, stay tuned for CTDNA and 427 00:28:57,040 --> 00:29:01,080 combination of new drugs and combination of new drugs, HTAC 428 00:29:01,080 --> 00:29:04,920 inhibitors and easy H2 inhibitors, both oral. 429 00:29:05,920 --> 00:29:09,200 So that is just some teasers for the next guidelines. 430 00:29:09,520 --> 00:29:10,960 OK, so there. Thanks a lot. 431 00:29:11,360 --> 00:29:14,440 Thank you to the audience for listening and if you enjoyed 432 00:29:14,440 --> 00:29:18,080 this episode, please like it and subscribe to our channel. 433 00:29:18,720 --> 00:29:21,520 Stay tuned for more episodes of EHA Unplugged.